Arch Biochem Biophys. 2008 Aug 15;476(2):107-12. Epub 2008 Feb 7. Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies?
Halliwell B.
Department of Biochemistry, National University of Singapore, University Hall, Lee Kong Chian Wing, UHL #05-02G, 21 Lower Kent Ridge Road, Singapore 119077, Singapore. bchbh@nus.edu.sg
Diets rich in polyphenols are epidemiologically associated with lower risk of developing some age-related diseases in humans. This apparent disease-protective effect of polyphenols is often attributed to their powerful antioxidant activities, as established in vitro. However, polyphenols can also exert pro-oxidant activities under certain experimental conditions. Neither pro-oxidant nor anti-oxidant activities have yet been clearly established to occur in vivo in humans, nor are they likely given the limited levels of polyphenols that are achievable in vivo after consumption of foods and beverages rich in them. Other actions of polyphenols may be more important in vivo. Many studies of the biological effects of polyphenols in cell culture have been affected by their ability to oxidise in culture media, and awareness of this problem can avoid erroneous claims.
PMID: 18284912 [PubMed - indexed for MEDLINE]
Altern Med Rev. 2009 Sep;14(3):226-46. Bioavailability and activity of phytosome complexes from botanical polyphenols: the silymarin, curcumin, green tea, and grape seed extracts.
Kidd PM.
Cell biology, University of California, Berkeley, USA. dockidd@dockidd.com
Plant-derived polyphenols are increasingly receiving attention as dietary supplements for the homeostatic management of inflammation, to support detoxication, and for anticancer, weight loss, and other benefits. Their pro-homeostatic effects on genes, transcription factors, enzymes, and cell signaling pathways are being intensively explored, but the poor bioavailability of some polyphenols likely contributes to poor clinical trial outcomes. This review covers four polyphenol preparations with poor bioavailability and their complexation into phytosomes to bypass this problem. Silybin and the other silymarin flavonolignans from milk thistle conserve tissue glutathione, are liver-protective, and have anticancer potential. Curcumin and its related diphenolic curcuminoids have potent antioxidant, anti-inflammatory, and anti-carcinogenic properties. The green tea flavan-3-ol catechins have antioxidant, anti-inflammatory, cardio- and neuro-protective effects, and anti-carcinogenic benefits, with fat oxidation effects coupled to weight loss. The complex grape seed proanthocyanidin mix (including catechin and epicatechin monomers and oligomers) counters oxidative stress and protects the circulatory system. For each of these preparations, conversion into phytosomes has improved efficacy without compromising safety. The phytosome technology creates intermolecular bonding between individual polyphenol molecules and one or more molecules of the phospholipid, phosphatidylcholine (PC). Molecular imaging suggests that PC molecule(s) enwrap each polyphenol; upon oral intake the amphipathic PC molecules likely usher the polyphenol through the intestinal epithelial cell outer membrane, subsequently accessing the bloodstream. PC itself has proven clinical efficacy that contributes to phytosome in vivo actions. As a molecular delivery vehicle, phytosome technology substantially improves the clinical applicabilities of polyphenols and other poorly absorbed plant medicinals.
PMID: 19803548 [PubMed - indexed for MEDLINE]
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A Specific Combination Of Ascorbic Acid, Lysine, Proline And Epigallocatechin Gallate Inhibits Proliferation And Extracellular Matrix Invasion Of Various Human Cancer Cell Lines FULL TEXT
Shrirang P Netke, M Waheed Roomi, Vadim Ivanov, Aleksandra Niedzwiecki* and Matthias Rath
We found that a specific combination of ascorbic acid (AA, 100µM), proline (P, 140 µM) and lysine (L, 400 µM) had a significant antiproliferative and antimetastatic effect against some human cancer cell lines, breast (MDA-MB-231), colon (HCT116) and skin (melanoma, A2058). In the presence of this nutrient combination the invasion of the extracellular matrix by human breast cancer cells, melanoma cells and colon cancer cells was inhibited by 50%, 10% and 30% respectively. Addition of epigallocatechin gallate (EGCG) further enhanced this nutritional synergy producing a more pronounced inhibitory effect on both cellular proliferation and matrix invasion. The proliferation of breast cancer cells MDA-MB-231 in the presence of AA, P, L and 20µg/ml of EGCG was reduced to 74% and colon cancer cells HCT116 to 69% compared to the unsupplemented medium. The increase in concentration of EGCG to 50µg/ml did not cause much further reduction in the number of breast cancer cells. However it reduced proliferation of colon cancer cells to 4,6% and melanoma cells to 30% of the control. Matrigel invasion by breast cancer cells and human melanoma cells in the presence of AA, P, L and 20µg/ml of EGCG was stopped completely. At a similar concentration, invasion by colon cancer cells was reduced to 24,9%. However, the expression of matrix metalloproteinases (MMPs) –2 and –9 was not altered by this nutrient combination in melanoma cells as visualized by gelatinase zymography. MMP-2 and MMP-9 were significantly inhibited by EGCG in a dose dependent manner, and L, P, AA have no additional effect. Thus the combination of AA, P, L and EGCG shows great potential for control of cancer using a safe and multi-targeted approach.
Quote:
The antiproliferative activity of the nutrient combinations used in these studies varied with the type of cancer cells. In breast cancer cells, the combination of AA, P and L with EGCG had higher anti-proliferative effects than when these nutrients were used individually
Combined resveratrol, quercetin, and catechin treatment reduces breast tumor growth in a nude mouse model.
Schlachterman A, Valle F, Wall KM, Azios NG, Castillo L, Morell L, Washington AV, Cubano LA, Dharmawardhane SF.
Department of Anatomy and Cell Biology, Universidad Central del Caribe School of Medicine, Bayamon, PR 00960, USA.
Grape polyphenols can act as antioxidants, antiangiogenics, and selective estrogen receptor (ER) modifiers and are therefore especially relevant for gynecological cancers such as breast cancer. The major polyphenols of red wine (resveratrol, quercetin, and catechin) have been individually shown to have anticancer properties. However, their combinatorial effect on metastatic breast cancers has not been investigated in vivo. We tested the effect of low dietary concentrations of resveratrol, quercetin, and catechin on breast cancer progression in vitro by analyzing cell proliferation and cell cycle progression. The effects of these compounds on fluorescently tagged breast tumor growth in nude mice were assessed using in situ fluorescence image analysis.
Individual polyphenols at 0.5 microM neither decreased breast cancer cell proliferation nor affected cell cycle progression in vitro. However, a combination of resveratrol, quercetin, and catechin at 0.5, 5, or 20 microM each significantly reduced cell proliferation and blocked cell cycle progression in vitro. Furthermore, using in situ image analysis, we determined that combined dietary polyphenols at 0.5, 5, or 25 mg/kg reduced primary tumor growth of breast cancer xenografts in a nude mouse model. Peak inhibition was observed at 5 mg/kg. These results indicate that grape polyphenols may inhibit breast cancer progression.
Biochem Biophys Res Commun. 2000 Jun 24;273(1):50-3. Artifacts in cell culture: rapid generation of hydrogen peroxide on addition of (-)-epigallocatechin, (-)-epigallocatechin gallate, (+)-catechin, and quercetin to commonly used cell culture media.
Long LH, Clement MV, Halliwell B.
Department of Biochemistry, Faculty of Medicine, National University of Singapore, 10 Kent Ridge Crescent, 119260, Singapore. There is considerable current interest in the possible beneficial health effects of quercetin, catechins, epigallocatechins, epigallocatechin gallates, and related phenolic compounds found in teas, wines, and other plant products. As a result, many laboratories are studying the effects of these compounds on cells in culture. The present paper shows that addition of these compounds to commonly used cell culture media leads to generation of substantial amounts of hydrogen peroxide (H(2)O(2)). Dulbecco's modified Eagle medium gives the highest H(2)O(2) level for all the compounds tested, with levels reaching >400 microM within 2 h for addition of 1 mM concentrations of gallic acid, epigallocatechin gallate, and epigallocatechin. Catechin and quercetin produced lower, but still significant, levels of H(2)O(2). McCoy's 5A and RPMI 1640 media also promoted H(2)O(2) production from the above phenolic compounds. This rapid generation of H(2)O(2) could account for some or all of the reported effects of phenolic compounds on cells in culture. Copyright 2000 Academic Press.
PMID: 10873562 [PubMed - indexed for MEDLINE]
Nutr Cancer. 2008;60(3):401-11.Links
Vitamin E analog alpha-TEA, methylseleninic acid, and trans-resveratrol in combination synergistically inhibit human breast cancer cell growth.
Snyder RM, Yu W, Jia L, Sanders BG, Kline K.
Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, Texas 78712-1097, USA.
Alpha-tocopherol ether-linked acetic acid analog [2,5,7,8-tetramethyl-2R-(4R, 8R-12-trimethyltridecyl) chroman-6-yloxyacetic acid (alpha-TEA)] is a novel form of vitamin E effective at killing cancer cells but not normal cells. alpha -TEA alone and together with methylseleninic acid (MSA) and trans-resveratrol (t-RES) were investigated for ability to induce apoptosis, DNA synthesis arrest, and cellular differentiation and inhibit colony formation in human MDA-MB-435-F-L breast cancer cells in culture. The 3 agents alone were effective in inhibiting cell growth by each of the 4 different assays, and 3-way combination treatments synergistically inhibited cell proliferation in each assay in comparison to individual treatments. Furthermore, combinations of alpha -TEA, t-RES, and MSA significantly enhanced levels of apoptosis in human breast (MDA-MB-231, MCF7, and T47D) and prostate (LnCaP, PC-3, and DU-145) cancer cell lines as well as in immortalized but nontumorigenic MCF10A cells but not primary cultures of human mammary epithelial cells. Western immunoblotting confirmed the induction of apoptosis in that the 3 agents induced poly(adenosine diphosphate-ribose) polymerase cleavage, with earlier detection and more complete cleavage seen in the combination treatment. Mechanistic studies showed combination treatments to inhibit cell proliferation via downregulation of cyclin D1 and induce apoptosis via activation of caspases 8 and 9 and downregulation of prosurvival proteins FLIP and survivin. In summary, the combination of alpha-TEA, MSA, and t-RES is more effective than single treatments for inhibiting cell proliferation, inducing cellular differentiation, and inducing cell death by apoptosis in human cancer cells in culture.
PMID: 18444175 [PubMed - indexed for MEDLIN
1: Eur J Gynaecol Oncol. 2001;22(5):347-9.Links
Herbal complex suppresses telomerase activity in chemo-endocrine resistant cancer cell lines.
Lian Z, Fujimoto J, Yokoyama Y, Niwa K, Tamaya T.
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Gifu City, Japan.
A herbal complex consisting of Hoelen, Angelicae radix, Scutellariae radix and Glycyrrhizae radix suppressed cell viability and telomerase activity in hormone-refractory and chemo-resistant cancer cell lines, namely poorly differentiated uterine endometrial cancer cell line AN3 CA, adriamycin-resistant breast cancer cell line MCF7/ADR and cisplatin-resistant ovarian cancer cell line A2780. Furthermore, the herbal complex suppressed the expression of the full length of human telomerase reverse transcriptase (hTERT), which is related to telomerase activity. This indicates that the herbal complex can suppress the tumor growth of chemoendocrine resistant cancers, at least in part via suppression of telomerase activity associated with down-regulated hTERT.
PMID: 11766737
Anticancer Res. 2009 Oct;29(10):3917-24. The effect of a novel botanical agent TBS-101 on invasive prostate cancer in animal models.
Evans S, Dizeyi N, Abrahamsson PA, Persson J.
Department of Clinical Sciences, Clinical Research Center, Lund University, University Hospital, 205 02, Malmo, Sweden.
Evans S, Dizeyi N, Abrahamsson PA, Persson J.
Department of Clinical Sciences, Clinical Research Center, Lund University, University Hospital, 205 02, Malmo, Sweden.
BACKGROUND: Traditional Botanical Supplement-101 (TBS-101) is a newly developed proprietary botanical agent containing seven standardized botanical extracts, including: Panax ginseng, cranberry, green tea, grape skin, grape seed, Ganoderma lucidum and chamomile. Each of the components has been consumed either in the regular diet or as natural supplement. When used as a single agent, each of these seven botanicals has been implicated in chemoprevention and therapy in various types of cancer. The anticancer effect of TBS-101, with the specific combination of these anti-cancer botanicals for the treatment of prostate cancer (PCa), has not been tested. MATERIALS AND METHODS: The IC(50) and the effect of TBS-101 on the proliferation and apoptosis of PC-3 cells were determined. Tumor xenograft mice were generated by subcutaneously implanting PC-3 cells into mice and tumors were allowed to grow to different sizes before starting the treatment. The effects of TBS-101 on tumor growth were assessed by measuring tumor size and by histological, pathological and immunohistochemical analyses. A basic toxicity study was performed to test the tolerance of the mice to high doses of TBS-101. RESULTS: Treatment of the PC-3 cells with TBS-101 resulted in a dose-dependent inhibition of cell growth, with an IC(50) of 1.4 microg/ml. A concomitant induction of apoptosis in PC-3 cells treated with TBS-101 was also observed. Upon the treatment with TBS-101, all three groups of mice bearing moderate or large tumors showed significant inhibition of tumor growth and invasion. In contrast, control mice treated with vehicle alone had significant tumor growth and lymph node metastasis. In the basic toxicity studies, high doses of TBS-101 exerted no toxicity in healthy or tumor-bearing mice. CONCLUSION: The natural botanical agent TBS-101 has a good safety profile and significant anticancer activities in hormone-refractory PC-3 cells and large aggressive PC-3 tumors in a xenograft mouse model and has great potential for the treatment of aggressive prostate cancer.
PMID: 19846929 [PubMed - indexed for MEDLINE]
Int J Oncol. 2009 Nov;35(5):1183-9. Fucoidan-Vitamin C complex suppresses tumor invasion through the basement membrane, with scarce injuries to normal or tumor cells, via decreases in oxidative stress and matrix metalloproteinases.
Saitoh Y, Nagai Y, Miwa N.
Cell-Death Control BioTechnology Laboratory, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara, Hiroshima 727-0023, Japan.
Fucoidan (Fucdn) and vitamin C (VC) were saturatedly dissolved in water and lyophilized and thoroughly ethanol-rinsed until no detection for supernatant vitamin C to form the Fucdn-VC (1:0.23 wt/wt) inclusion body (Fucdn-VC-IB). Fucdn-VC-IB increased not only VC-stabilizing at 37 degrees C, but also hydroxyl-radical scavenging as shown by ESR/spin-trap method, more markedly than a mere mixture of Fucdn:VC (1:0.23 wt/wt). Invasion of human fibrosarcoma cells HT-1080 through the basement membrane was repressed by Fucdn-VC-IB of non-cytotoxic concentrations without significant inhibition to human skin dermal fibroblasts DUMS-16 cells. Fucdn-VC-IB suppressed the invasiveness-related gelatinases MMP-2/9, and diminished reactive oxygen species inside the cytoplasm around the nucleus, in HT-1080 cells as shown by electrophoretic zymography and the redox indicator NBT assay, respectively. Thus Fucdn-VC-IB markedly exhibits antioxidant and MMP-suppressing activities and preferentially inhibited tumor invasion without cytotoxicity to normal cells, and is suggested as a potent tumor-invasion suppressor.
PMID: 19787274 [PubMed - indexed for MEDLINE]
Oncol Rep. 2009 Nov;22(5):1077-83. A traditional Chinese medicine formulation consisting of Rhizoma Corydalis and Rhizoma Curcumae exerts synergistic anti-tumor activity.
Gao JL, He TC, Li YB, Wang YT.
Institute of Chinese Medical Sciences, University of Macau, Macau 999078, PR China.
Synergy analysis of anticancer agents is an important approach to determining the ratio and/or dose of drugs for clinical combination therapy. However, this method is rarely used to evaluate the composition of traditional Chinese medicine formulation. 'Yanhusuo San' (YHSS), which consists of yanhusuo (Rhizoma Corydalis) and Ezhu (Rhizoma Curcumae), has been an archaic Chinese medicine prescription since the Song dynasty (960-1279 AD). We previously demonstrated that either yanhusuo or ezhu has strong anticancer effect. Herein, we sought to determine the possible synergic effect between these two Chinese herbs. We measured the IC50 of each herb extract and both extracts at different ratios of doses by MTT assay. Isobologram and combination index (CI) analyses were used to evaluate the synergistic effect of yanhusuo and ezhu in different fixed ratios. Our results indicated that a combination of two herbal extracts exhibits the strongest anticancer cell proliferation effect at the ratio of 3:2 (ezhu to yanhusuo; referred to as E3Y2). Using Boyden Chamber assay, flow cytometry, and fluorescence microscopy analysis, we found that E3Y2 could markedly reduce the cell invasion ability and induce cytochrome c release rather than single use, but E3Y2 could not influence the cell cycle distribution. When the levels of ERK1/2, p-ERK1/2 and p-Rb were determined by Western blot analysis, we found that the E3Y2 significantly suppresses the level of p-ERK. Thus, our studies provide a plausible molecular basis of the synergistic anti-tumor effect of ezhu and yanhusuo.
PMID: 19787224 [PubMed - indexed for MEDLINE]
Am J Chin Med. 2005;33(3):381-95. Immunomodulatory activities of Yunzhi and Danshen in post-treatment breast cancer patients.
Wong CK, Bao YX, Wong EL, Leung PC, Fung KP, Lam CW.
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR. China.
Breast cancer is the most common cancer among women worldwide. Discomfort and fatigue are usually arisen from anticancer therapy such as surgery, radiotherapy, chemotherapy, hormonal therapy, or combination therapy, because of the suppressed immunological functions. Yunzhi (Coriolus versicolor) can modulate various immunological functions in vitro, in vivo, and in human clinical trials. Danshen (Salvia miltiorrhiza) has been shown to benefit the circulatory system by its vasodilating and anti-dementia activity. The purpose of this clinical trial was to evaluate the immunomodulatory effects of Yunzhi-Danshen capsules in post-treatment breast cancer patients. Eighty-two patients with breast cancer were recruited to take Yunzhi [50 mg/kg body weight, 100% polysaccharopeptide (PSP)] and Danshen (20 mg/kg body weight) capsules every day for a total of 6 months. EDTA blood samples were collected every 2 months for the investigation of immunological functions. Flow cytometry was used to assess the percentages and absolute counts of human lymphocyte subsets in whole blood. Plasma level of soluble interleukin-2 receptor (sIL-2R) was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that the absolute counts of T-helper lymphocytes (CD4+), the ratio of T-helper (CD4+)/T suppressor and cytotoxic lymphocytes (CD8+), and the percentage and the absolute counts of B-lymphocytes were significantly elevated in patients with breast cancer after taking Yunzhi-Danshen capsules, while plasma slL-2R concentration was significantly decreased (all p < 0.05). Therefore, the regular oral consumption of Yunzhi-Danshen capsules could be beneficial for promoting immunological function in post-treatment of breast cancer patients.
Am J Chin Med. 2008;36(4):729-44. Green tea extract enhances the selective cytotoxic activity of Zizyphus jujuba extracts in HepG2 cells.
Huang X, Kojima-Yuasa A, Xu S, Norikura T, Kennedy DO, Hasuma T, Matsui-Yuasa I.
Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka 558-8585, Japan.
Anticarcinogenic effects attributed to phytochemicals may be based on synergistic, additive, or antagonistic interactions of many compounds. In our previous study, we demonstrated that the chloroform fraction (CHCl(3)-F) from Z. jujuba has anticancer activity in HepG2 cells. In China, many people drink jujuba tea and believe in the synergic effects of jujuba and tea for better health.We therefore investigated the effects of CHCl(3)-F and green tea extract (GTE), and their underlying mechanisms of action in HepG2 cells. Our results showed that GTE enhanced the effect of CHCl(3)-F on cell viability in HepG2 cells, without cytotoxicity in rat hepatocytes, which was used as a normal cell model. Furthermore, combination of CHCl(3)-F and GTE caused an effect on G1 phase arrest but not on apoptosis. Interestingly, the mechanism of the G1 arrest was associated, not with an increase in p27(Kip1) levels and the hypohosphorylation of Rb, which are pathways used by CHCl(3)-F on G1 arrest in HepG2 cells, but with increases in p53 and p21(Waf1/Cip1) levels, and a decrease in cyclin E levels. Collectively, our findings suggest that combination of CHCl(3)-F and GTE produces an enhanced cell growth inhibition effect, and that the resultant G1 arrest was caused via a different mechanism as that of CHCl(3)-F treatment alone.
Recently concluded preliminary tests at Purdue University using cancer cells in culture have shown that the synergistic formulation of Capsibiol-T inhibits tNOX. When tNOX activity is inhibited, cancer cells fail to grow to the size required for division and undergo programmed cell death (apoptosis). Capsibiol-T® is a unique, synergistic formulation of modified capsaicin and decaffeinated green tea. Before the proprietary process to modify capsaicin for exclusive use in Capsibiol-T® was developed, the dosage required for capsaicin to be effective (its therapeutic dosage) had exceeded the level at which its pungency and neurological discomfort could be tolerated.The amount of modified capsaicin (12.5mg per capsule) in synergy with decaffeinated green tea (637.5mg per capsule) enables Capsibiol-T® to achieve a ten-fold increase in potency. The synergistic combination of Capsibiol-T® is 10 times more potent than either green tea or capsaicin separately. In an effort to provide the greatest benefit, Capsibiol-T® should be taken three times daily, one capsule every eight hours.
Green tea appears to block growth of new blood vessels that tumors require for growth and metastasis.
Green tea catechin EGCg inhibits special enzyme cancer cells secrete to penetrate and colonize tissue.
Green tea enhances the effectiveness of conventional therapies.
EGCg inhibits telomerase, the enzyme that "immortalizes" cancer cells.
At the University of California at Berkeley, the Chairman of the Nutritional Sciences Department and the Director of the National Institutes of Health Cancer Research Program were studying the anticancer properties of Diindolylmethane (DIM), a naturally occurring compound found in Brassica vegetables (broccoli, cauliflower, cabbage, kale, brussels sprouts), when they made a remarkable discovery: DIM is a potent activator of the immune response system. Activation of the immune system in part explains DIM's anticancer properties, and for the first time, sheds light on its potent antiviral and antibacterial properties.The scientists patented their discovery and ActivaMune was launched as a first-in-class nutritional supplement to enhance the immune system and support multiple organs throughout the body: breast, prostate, cardiovascular, vision, skin and colon health. ActivaMune's unique and patented formula combines multiple nutrients for maximum effectiveness: Diindolylmethane (DIM), Sulforaphane, Selenium, Lycopene, Lutein, Zeaxanthin, Calcium and Vitamins C, D3 & E.
ActivaMune's formula is exclusively licensed from the University of California at Berkeley. The supplement provides phytonutrients equivalent to approximately five pounds of fresh organic uncooked broccoli, tomatoes and spinach per day. All broccoli extract supplements on the market today, without exception, do not have the active ingredients in ActivaMune as their manufacturing process (heat or freeze drying) destroys the enzyme necessary for the production of the key phytonutrients present in this supplement.
Nutr Cancer. 2007;57(1):78-87. Zyflamend, a polyherbal preparation, inhibits invasion, suppresses osteoclastogenesis, and potentiates apoptosis through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene products.
Sandur SK, Ahn KS, Ichikawa H, Sethi G, Shishodia S, Newman RA, Aggarwal BB.
Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. Zyflamend, a polyherbal preparation, was designed based on constituents that exhibit antiproliferative, antiinflammatory, antioxidant, antiangiogenic, and apoptotic activities through a mechanism that is not well defined. Because the nuclear factor (NF)-kappaB has been shown to regulate proliferation, invasion, and metastasis of tumor cells, we postulated that Zyflamend modulates the activity of NF-kappa B. To test this hypothesis, we examined the effect of this preparation on NF-kappaB and NF-kappaB-regulated gene products. We found that Zyflamend inhibited receptor activator of NF-kappa B ligand-induced osteoclastogenesis, suppressed tumor necrosis factor (TNF)-induced invasion, and potentiated the cytotoxicity induced by TNF and chemotherapeutic agents, all of which are known to require NF-kappa B activation. Zyflamend suppressed NF-kappa B activation induced by both TNF and cigarette smoke condensate. The expression of NF-kappa B-regulated gene products involved in antiapoptosis (inhibitor-of-apoptosis protein 1/2, Bcl-2, Bcl-xL, FADD-like interleukin-1betaconverting enzyme/caspase-8 inhibitory protein, TNF receptor-associated factor-1, and survivin) and angiogenesis (vascular endothelial growth factor, cyclooxygenase-2, intercellular adhesion molecule, and matrix metalloproteinase-9) was also down-regulated by Zyflamend. This correlated with potentiation of cell death induced by TNF and chemotherapeutic agents. Overall, our results indicate that Zyflamend suppresses osteoclastogenesis, inhibits invasion, and potentiates cytotoxicity through down-regulation of NF-kappa B activation and NF-kappa B-regulated gene products.
PMID: 17516865 [PubMed - indexed for MEDLINE]
Curr Med Chem. 2009;16(12):1451-62. Chemoprotective mechanism of the natural compounds, epigallocatechin-3-O-gallate, quercetin and curcumin against cancer and cardiovascular diseases.
Jagtap S, Meganathan K, Wagh V, Winkler J, Hescheler J, Sachinidis A.
Center of Physiology and Pathophysiology, University of Cologne, Germany.
Cancer and cardiovascular disease (CVD) chemoprevention can be achieved by the use of natural, synthetic, or biologic compounds to reverse, suppress, or prevent the development of diseases. Chemoprevention is a potential anti-cancer approach, which has reduced secondary effects in comparison to classical prophylaxis. Natural compounds such as flavonoids reduce oxidative stress, which is the most likely mechanism in the protective effects of these compounds. Even though the exact mechanisms of action are not well understood another central action mechanism of polyphenolic flavonoids seems to be an induction of apoptosis as demonstrated in numerous cellular systems. Moreover, flavonoids may modulate protein and lipid kinase signaling pathways. Understanding the mechanism of these natural products will contribute to the development of more specific preventive strategies against cancer and CVD. Much of the research in the field is focused on epigallocatechin-3-O-gallate (EGCG), quercetin and curcumin, which were found to have beneficial effects against cancer and CVD. We review the chemoprotective mechanisms through which these natural compounds exert their beneficial effects against cancer and CVDs.
PMID: 19355899 [PubMed - indexed for MEDLINE]
Free Radic Res. 2002 May;36(5):593-9. Hydrogen peroxide generation in caco-2 cell culture medium by addition of phenolic compounds: effect of ascorbic acid.
Roques SC, Landrault N, Teissèdre PL, Laurent C, Besançon P, Rouane JM, Caporiccio B.
Unité Nutrition, Laboratoire Génie Biologique et Sciences des Aliments, Université Montpellier II, France.
Phenolic compounds have recently attracted special attention due to their beneficial health effects; their intestinal absorption and bioavailability need, therefore, to be investigated and Caco-2 cell culture model appeared as a promising tool. We have shown herein that the addition of a grape seed extract (GSE) to Dulbecco's modified Eagle's medium (DMEM) used for Caco-2 cell culture leads to a substantial loss of catechin, epicatechin and B2 and B3 dimers from GSE in the medium after 24 h and to a production of hydrogen peroxide (H2O2). When 1420 microM ascorbic acid is added to the DMEM, such H2O2 production was prevented. This hydrogen peroxide generation substantially involves inorganic salts from the DMEM. We recommend that ascorbic acid be added to circumvent such a risk.
International Classes: A01N65/00; A61K36/258; A61K36/481; A61K36/236; A61K36/355; A61K36/00; A61K36/254; A61K36/48
Foreign References:
CN1220891
June, 1999
CN1421224
June, 2003
CN1470276
January, 2004
JP360025933
February, 1985
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095136827; Taiwan Office Action; May 2, 2008; Taiwan.
Primary Examiner:
Meller, Michael V.
Assistant Examiner:
Mi, Qiuwen
Attorney, Agent or Firm:
WPAT, PC
King, Anthony
Claims:
What is claimed is:
1. A composition consisting of Wubeizi, Lonicera japonica, Astragalus membranaceus, Rehmanniae Radix, Glycyrrhizae Radix and Panax ginseng, wherein weight ratios of any two components range from 1:10 to 10:1; wherein Wubeizi is a gall produced by parasitic aphids Melaphis chinensis (Bell) Baker on a leave or stem of a plant selected from the group consisting of Rhus chinensis Mill, Rhus potaninii Maxim and Rhus punjabensis Stew. var. sinica (Diels) Rehd. et Wils.; wherein Lonicera japonica is prepared from flower buds of a plant selected from the group consisting of Lonicera japonica and Lonicera confuse, wherein Astragalus membranaceus is prepared from a root of a plant selected from the group consisting of Astragalus membranaceus (Fisch.) Bge. and Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao; wherein Rehmanniae Radix is prepared from a root of Rehmannia glutinosa Libosch; wherein Glycyrrhizae Radix is prepared from a whole plant of a plant selected from the group consisting of Glycyrrhiza uralensis Fisch., Glycyrrhiza glabra L., Glycyrrhiza kansuensis Chang et Peng and Glycyrrhiza inflata Batal; and wherein Panax ginseng is prepared from the root of a plant selected from a group consisting of Panax ginseng and Panax pseudoginseng.
2. The composition of claim 1, wherein weight ratios of any two components range from 1:5 to 5:1.
3. The composition of claim 2, wherein weight ratios of any two components range from 1:3 to 3:1.
4. The composition of claim 3, wherein weight ratios of any two components are 1:1.
Description: FIELD OF THE INVENTION
The present invention relates to a herbal composition for treating cancer, especially for breast cancer. BACKGROUND OF THE INVENTION
The popularity of traditional herbal medicine being used as complementary medicines or alternative medicines is rapidly increasing in recent years. The current understanding on the molecular mechanisms of immunopotentiating polysaccharides from medicinal herbs have provided important clues on the anti-cancer effects of Chinese herbal medicines [Shao BM, et al., Biochem Biophys Res Commun. 2004 Aug. 6;320(4):1103-11]. Also, it was found that the combination of anticancer drugs with some herbal extracts contributes to the enhancement of clinical outcomes in cancer chemotherapy [Takara K, et al., Biol Pharm Bull. 2005 Jan.; 28(1):138-42]. Chinese herbal medicines have emerged as an effective tool for treating cancer.
In previous publications, several herbal compounds or complexes have been indicated to be candidate drugs for treating breast cancer. For example, the Glycyrrhizae radix extract was suggested to exhibit inhibitory effects on E2-related endometrial carcinogenesis in mice [Niwa K. et al., Jpn J Cancer Res. 1999 Jul.; 90(7):726-32]. A herbal complex consisting of Hoelen, Angelicae radix, Scutellariae radix and Glycyrrhizae radix suppresses the tumor growth of chemoendocrine resistant cancers [Lian Z, et al., Eur J Gynaecol Oncol. 2001; 22(5): 347-9]. Still another herbal complex consisting of Hoelen, Angelicae radix, Scutellariae radix and Glycyrrhizae radix is shown to be a potential candidate for treating endocrine-resistant gynecologic carcinomas [Lian Z, et al., Cancer Detect Prev. 2003;27(2):147-54]. In addition, it is suggested that Puerariae radix and Ginseng radix Rubra extracts have effective estrogenic actions and could be developed as estrogenic supplements [Kim OS, et al., Arch Pharm Res. 2004 Sep.;27(9):906-11]. Furthermore, the complex named Zhu-xiang containing ginseng and Carthamus tinctorius also exhibits the ability to inhibit proliferation in MDA-MB-231 breast cancer cell [Loo WT, et al., Life Sci. 2004 Nov. 26;76(2):191-200]. These herbal medicines have shed some lights on the therapy of breast cancer.
All of the above-mentioned references are herein incorporated by reference in their entireties. SUMMARY OF THE INVENTION
The present invention relates to a herbal composition, comprising wubeizi, Lonicera japonica, Astragalus membranaceus, Rehmanniae Radix, Glycyrrhizae Radix and Panax schinseng . The weight ratios of any two components range from 1:10 to 10:1. BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows the inhibitory effects of the composition of the present invention, Taxol and Doxorubicin on cell growth of human cancer cell A498, HCT 116, Hep 3B, LNCaP clone FGC, MCF-7, MKN45, NCI-H226, NPC-TW01 and the human normal renal cell RPTEC.
FIG. 2 shows the morphological effects of the composition of the present invention, Taxol and Doxorubicin on human cancer cell A498, HCT 116, Hep 3B, LNCaP clone FGC, MCF-7, MKN45, NCI-H226, NPC-TW01 and the human normal renal cell RPTEC. DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to a herbal composition that provides anti-cancer effects, especially for breast cancer.
Herbal Composition
The present invention relates to a composition of herbal medicines comprising Wubeizi, Lonicerajaponica, Astragalus membranaceus, Rehmanniae Radix, Glycyrrhizae Radix and Panax schinseng.
Wubeizi is the gall produced by the parasitic aphids Melaphis chinensis (Bell) Baker on the leaves or stems of a plant selected from the group consisting of Rhus chinensis Mill, Rhus potaninii Maxim and Rhus punjabensis Stew. var. sinica (Diels) Rehd. et Wils. Lonicera japonica is prepared from the flower buds of a plant selected from the group consisting of Lonicerajaponica and Lonicera confuse. Astragalus membranaceus is prepared from the roots of a plant selected from the group consisting of Astragalus membranaceus (Fisch.) Bge. and Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao. Rehmanniae Radix is prepared from the roots of Rehmannia glutinosa Libosch. Glycyrrhizae Radix is prepared from the whole plant of a plant selected from the group consisting of Glycyrrhiza uralensis Fisch., Glycyrrhiza glabra L., Glycyrrhiza kansuensis Chang et Peng and Glycyrrhiza inflata Batal. Panax schinseng is prepared from the roots of a plant selected from the group consisting of Panax schinseng and Panax pseudoginseng.
The weight ratios of any two components in the composition of the present invention range from 1:10 to 10:1. In a preferred embodiment, the weight ratios of any two components range from 1:7 to 7:1. In a more preferred embodiment, the weight ratios of any two components range from 1:5 to 5:1. In a furthermore preferred embodiment, the weight ratios of any two components range from 1:3 to 3:1. In the most preferred embodiment, the weight ratio of wubeizi, Lonicerajaponica, Astragalus membranaceus, Rehmanniae Radix, Glycyrrhizae Radix and Panax schinseng is 1:1:1:1:1:1.
Anti-cancer Effects
The present composition can induce the apoptosis of the cancer cell in accordance with this invention. The cancer cells include abnormal cancer cells associated with lymphoma, leukemia, plasma cell dyscrasias, multiple myeloma, amylodosis, also as known as hepatocellular cancer, colorectal cancer, renal cancer, breast cancer, prostate cancer, stomach cancer, lung cancer, nasal-pharyngeal cancer, ovarian cancer, bone cancer, gastric cancer, pancreatic cancer, and melanoma. In a preferred embodiment, the present composition can induce apoptosis of the tumor cells of hepatocellular cancer, colorectal cancer, renal cancer, breast cancer, prostate cancer, stomach cancer, lung cancer and nasal-pharyngeal cancer. In the most preferred embodiment, the present composition induces apoptosis of breast cancer cells. EXAMPLES
The examples below are non-limiting and are merely representative of various aspects and features of the present invention. Example 1
Preparation of Single-herb Herbal Medicines
A whole herb of medicinal plant was obtained, washed with cold water and dried. The plant materials were then extracted with boiling water. The weight ratio of plant material to water was approximately 1:5 to 1:10. The amount of water used should at least cover the plant material in the extraction vessel. To allow effective extraction of the desired components, samples were boiled for 0.5 to one hour, but not more than 3 hours. Then, the aqueous solution was separated from the plant residues by filtration. After that, the aqueous solution was spray-dried, freeze-dried or absorbed by powdered material of starch. The single-herb herbal medicine was prepared in powdered form. Example 2
Preparation of the Composition of the Invention
The herb mixture was prepared by mixing six single-herb herbal medicines wubeizi, Lonicera japonica, Astragalus membranaceus, Rehmanniae Radix, Glycyrrhizae Radix and Panax schinseng at a ratio of 1:1:1:1:1:1 by weight. The resulted mixture was the composition of the present invention. Example 3
Anti-cancer Testing of the Herb Mixtures
Cell Lines
To examine the effects of the present composition SF-01 on inhibition of cancer/tumor cells, various human cell lines were used, including one normal cell line and eight cancer/tumor cell lines:
1. RPTEC (Cambrex): Normal renal proxima tubule epithelial cell, Human
2. A-498 (ATCC HTB-44): Kidney carcinoma, Human
3. HCT 116 (ATCC CCL-247): Colorectal carcinoma, Human
4. Hep 3B (ATCC HB-8064): Hepatocellular carcinoma, Human
5. LNCap clone FGC (ATCC CRL-1740): Prostate carcinoma, Human
6. MCF-7 (ATCC HTB-22): Mammary gland adenocarcinoma, Human
7. MKN45 (FDSC JCRB0245): Stomach carcinoma, Human
8. NCI-H226 (ATCC CRL-5826): Lung carcinoma, Human
9. NPC-TW01 (School of Medicine, NTU): Nasal-pharyngeal carcinoma, Human
All of the cell lines used were negative for mycoplasma test. Among these cell lines, renal proximal tubule epithelial cell (RPTEC), the only normal cell line, were maintained in REGM™ BulletKit at 37° C. in a humidified atmosphere of 5% CO 2 /95% air, in the absence of antibiotics according to the manufacture's recommendation. On the other hand, the eight tumor cell lines were maintained in DulBeccco's modified essential medium (DMEM) supplied with 10% fetal bovine serum at 37° C., in a humidified atmosphere of 5% CO 2 /95% air in the absence of antibiotics.
Reagents
Fetal calf serum was purchased from BioWhittaker(Walkersville, Md.), MTS was obtained from Promega (Madison, Wis.). All of the other chemicals were from Sigma Chemical (St. Louis, Mo.) and were standard analytic grade or higher. SF-01 was dissolved in the complete culture medium at final concentration of 10mg/ml and was filter sterilized. Doxorubicin and Taxol were prepared in DMSO at concentration of 20 mM and were used as the positive controls.
To evaluate the antitumoral activity of SF-01 towards various human cancer cell lines and measure the potential cytotoxicity of SF-01 towards the primary human renal cell lines (RPTEC), an in vitro cytotoxicity assay was carried out. Tumor cells were seeded at a density of 2×10 3 to 8×10 3 cells/well in 96-well plate 16 hours prior to the chemicals treatment. After exposure to different concentrations of SF-01 (5.0 to 0.0016 mg/ml), Doxorubixin (10 μM to 3.2 nM) or Taxol (2 μM to 0.02 nM) for 72 hours, cells were washed, replaced with medium containing 0.4mg/MTS [3-(4,5-dimethythiazol-2-yl)-5-(3-carboxymethosyphenyl)-2-(4 -sulfophenyl)-2H-tetrazolium] and further incubated for 2 hours. To quantify the metabolically viable cells, the conversion of MTS to formazan was measured by absorbance at 490 nm in a 96-well microtiter plate reader. The mock-treated control was used to evaluate the effect of the chemical on cell growth and to determine the concentration of chemical that inhibited 50% of cell growth (IC 50 ). The percentage of cytostasis was calculated by the formula:
Cytostasis (%)=[1−(B/A)]×100,
where A is the absorbance of the untreated control and B is the absorbance of the treated cell.
To evaluate the effects of the tested drugs on cell growth, the concentration of chemical that caused 50% reduction of the treated cells (IC 50 ) was calculated from the dose response curve (FIG. 1) for each cell line. The IC 50 for both Doxorubicin and Taxol to various human tumor cellines were found between 800 to 11 nM and 11 to 0.003 nM (Table 1) respectively, which was consistent with previously data. Our data showed that the cytotoxicity of SF-01 toward cancer cell line depends on the nature of the tumor cells, showing the selectivity of SF-01. Among all the tumor cell lines tested, MCF-7 was found to be most sensitive to SF-01, as the concentration of SF-01 as low as 0.59 mg/ml was able to cause 50% reduction of the treated cells, demonstrating the efficient anti-tumor activity of SF-01 on breast cancer cells. On the other hand, no noticeable morphological change or cytotoxicity was found when the normal cell line RPTEC was cultured with SF-01 for 72 hours compared to the untreated cells (FIG. 2). In addition, cell growth stimulation was found when RPTEC was cultured in higher concentration of SF-01. The results showed that SF-01 has little or no toxicity to the normal cells and also might promote its growth at higher concentration. This report was finished from Department of Toxicology and Preclinical Sciences, Pharmaceutical R&D Laboratories, Development Center for Biotechnology. No. 103, Lane 169, Kang Ning St. Hsichih city, Taipei county, Taiwan.
TABLE 1
The concentration of SF-01, Taxol and Doxorubicin that
inhibit 50% of cell growth (IC 50 ) of human cancer cell
A498, HCT 116, Hep 3B, LNCaP clone FGC, MCF-7, MKN45,
NCI-H226, NPC-TW01 and the human normal renal cell RPTEC.
Rejuvenation Res. 2006 Spring;9(1):45-55. Catechin-vanilloid synergies with potential clinical applications in cancer.
Morré DM, Morré DJ.
Department of Foods and Nutrition, Purdue University, West Lafayette, Indiana 47907-2059, USA. morredm@purdue.edu A cancer-specific cell surface protein, tNOX, has been identified as a target for low-dose cell killing (apoptosis) of cancer cells by green tea catechins and Capsicum vanilloid combinations. This protein is uniquely associated with all forms of cancer and is absent from normal cells and tissues. Its activity is correlated with cancer growth. When blocked, cancer cells fail to enlarge after division and eventually die. Among the most potent and effective inhibitors of tNOX are naturally occurring polyphenols exemplified by the principal green tea catechin (-)-epigallocatechin gallate (EGCg) and the vanilloid capsaicin. Catechin-vanilloid combinations are 10 to 100 times more effective than either catechins or vanilloids alone. Vector-forced overexpression of tNOX cDNA and antisense has demonstrated that the tNOX target is both necessary and sufficient to explain the anticancer properties of green tea catechins alone and in vanilloid-containing combinations. The necessity and sufficiency of tNOX was validated as the catechin target with transgenic mice overexpressing the processed form of tNOX. Transgenic mice grew faster and the increased growth caused by tNOX overexpression was blocked by EGCg in the drinking water. A catechin-vanilloid mixture where one 350-mg capsule is equivalent to 16 cups of green tea in its ability to inhibit tNOX and growth of cancer cells in culture is undergoing clinical evaluation as a therapeutic aid for cancer patients.
PMID: 16608395 [PubMed - indexed for MEDLINE]
Cancer Metastasis Rev. 2010 Sep;29(3):529-42. Micronutrient synergy-a new tool in effective control of metastasis and other key mechanisms of cancer. Niedzwiecki A, Roomi MW, Kalinovsky T, Rath M.
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA, 95050, USA, author@drrath.com.
Abstract
Consumption of a plant-based diet has been associated with prevention of the development and progression of cancer. We have developed strategies to inhibit cancer development and its spread by targeting common mechanisms used by all types of cancer cells that decrease stability and integrity of connective tissue. Strengthening of collagen and connective tissue can be achieved naturally through the synergistic effects of selected nutrients, such as lysine, proline, ascorbic acid and green tea extract (NM). This micronutrient mixture has exhibited a potent anticancer activity in vivo and in vitro in a few dozen cancer cell lines. Its anti-cancer effects include inhibition of metastasis, tumor growth, matrix metalloproteinase (MMP) secretion, invasion, angiogenesis, and cell growth as well as induction of apoptosis. Many cancers are often diagnosed at later stages, when metastasis has occurred, which standard treatment has been unable to control. Our studies on NM effects on hepatic and pulmonary metastasis demonstrated profound, significant suppression of metastasis in a murine model.Evaluation of effects of NM on xenografts in murine models demonstrated significant reduction in tumor size and tumor burden in all human cancer cell lines tested. In vitro studies demonstrated that NM was very effective in inhibition of cell proliferation (by MTT assay), MMP secretion (by gelatinase zymography), cell invasion (through Matrigel), cell migration (by scratch test), induction of apoptosis (by live green caspase) and induction of pro-apoptotic genes in many diverse cancer cell lines. Furthermore, in vivo and in vitro studies of effects of individual micronutrients compared to their specific combination demonstrated synergistic effects resulting in improved anticancer potency.
PMID: 20717705 [PubMed - in process]
InflamAway is a high quality, scientifically supported herbal formulation designed to modulate inflammation via multiple pathways throughout the body by optimizing immune function, the stress response, and the removal of damaging toxins.
This high potency herbal formula targets multiple pro-inflammatory pathways and activators of the inflammatory cascade (Cox-2, Lox-5, 12 and 15, NF-KB, Bcl-2) to assist in cellular homeostasis and allostasis.
Inflammation is present in everyones body as a natural byproduct of many normal physiological activities, and is also an essential part of the healing process. It is often referred to as a cascade or a cycle due to its self-promoting nature.
Natura’s “Inflam-Away”, is a formula made up of a powerful combination of unique and potent herbal
extracts designed to aid the body at the deepest level by controlling multiple, well-defined proinflammatory
pathways. These pathways are often up-regulated in disease states, especially cancer,
arthritis, and auto-immune diseases, such as colitis, scleroderma, and rheumatism. The formula
combines state-of-the-art concentrated extracts from several botanical sources to achieve therapeutic
results. The biomedical concepts behind the formulation are based on contemporary research that
elucidates the effects and components of specific herbs and compounds as they pertain to cell response
and inflammation. This modern biomedical information is combined with the traditional medical
knowledge of the source plants to create synergy and balance within the formulation.
Inflammation is a by product of many of the body’s physiological processes, and it is an essential part of
the healing process. However, the inflammatory process is a cascade of biochemical events that once in
motion can become a vicious cycle of self destruction. Within the human body, there are proinflammatory
and anti-inflammatory chemical messengers that regulate the inflammatory response.
These agents act as on/off switches for our inflammatory processes. The body has mechanisms in place
that inhibit the inflammatory cascade, for instance, the release of endogenous cortisone from the adrenal
cortex. As well, there are mechanisms that promote the inflammatory cascade, such as the release of
acute phase mediators into the tissue surrounding an abrasion or into the blood stream following
exposure to an environmental toxin. This incredibly complex biological system is influenced by
countless factors, both endogenous and exogenous.
Inflam-Away targets many key, pro-inflammatory pathways and aids the body in regulating the
inflammatory response. Inflam-Away is designed to reduce inflammation through the regulation of
many of the body’s most powerful pro-inflammatory systems including COX-2, LOX-5 and 12,
NFkappa beta, TNF alpha, iNOS, etc. The symptoms associated with many diseases are strongly
influenced by up-regulated inflammatory pathways. There is extensive evidence in support of the theory
that chronic inflammation leads to an increased cancer risk. Most cancers are known to occur more
frequently in people with certain well-known inflammatory diseases, such as inflammatory bowel
disease, hepatitis, or autoimmune conditions. High levels of inflammation, a result of such things as
viruses, asbestos exposure, obesity, and increased levels of stress in general, leads to oxidative damage.
The oxidative damage in turn leads to the development of genetic transcription errors, and ultimately
dysfunction at the cellular, organ, and organ system levels.
Feverfew (Tanacetum parthenium)
Inflam-Away assists in protecting the body from the proliferative effects of inflammation by modulating
apoptotic regulatory responses, such as the down-regulation of NF-kB (promotes inflammation) and
Bcl-2 (prevents apoptosis).
Feverfew is well known for its ability to prevent migraine headaches. Most researchers attribute the
herb’s (Feverfew’s) anti-migraine/anti-inflammatory properties to the presence of the sesquiterpene
lactone, parthenolide, which hinders the inflammatory process, or to the release of serotonin from
certain white blood cells and platelets, which in turn can reduce the frequency and severity of migraines
by keeping blood vessels properly toned. Feverfew also interferes with the actions of arachidonic acid
and histamine, which can contribute to migraine pain and other symptoms, as well as be involved in
other diseases including cancer.
Feverfew inhibits certain pro-inflammatory signaling pathways. The sesquiterpene lactone from
feverfew, Parthenolide, at .8% concentration, dose-dependently increased the amount of NF-kB
inhibitory protein, thus lowering relative NF-kB expression. Furthermore, recent research states that
parthenolide destroys acute myeloid leukemia (AML) cells, leaving normal bone marrow cells relatively
unscathed. Moreover, the compound may get at the root of the disease because it also kills stem cells
that give rise to AML.
Boswellia (Boswellia serrata)
Inflam-Away features a very potent form of the ancient herb known as Frankincense, or Boswellia
serrata. Boswellia has been used for thousands of years to treat conditions characterized by
inflammation. In TCM, (Traditional Chinese Medicine) it has been classified as an herb that promotes
blood circulation and promotes the regeneration of tissue. Boswellin® Super is a potent boswellia
extract, standardized to provide a high concentration of the important LOX-5 inhibitor, AKBA (3-Oacetyl-
11-keto-beta-boswellic acid) as well as an array of pentacyclic triterpenes called boswellic acids.
LOX-5 is known to promote the synthesis of leukotrienes, one of the body’s most potent stimulators of
inflammation. Boswellic acids have been shown to preferentially inhibit COX-2, as well as 5, 12, and
15-lipoxygenase. This combination of a super concentrate of AKBA and boswellic acids, effectively
targets key, pro-inflammatory signaling compounds involved in the process of inflammation.
Gum resin extracts of Boswellia species have been traditionally applied in folk medicine for centuries to
treat various chronic inflammatory diseases, and experimental data from animal models and studies with
human subjects confirmed the potential of Boswellia species extracts for the treatment of not only
inflammation but also of cancer. Analysis of the ingredients of these extracts revealed that boswellic
acids possess biological activities and appear to be responsible for the respective pharmacological
actions.
Magnolia bark (Magnolia officinalis)
Magnolia bark is known for its aromatic properties and has been used for thousands of years in TCM to
resolve digestive problems caused by the “stagnation of Qi”. Magnolia bark’s anti-stress benefits appear
to be related to its ability to afford the body better control of the stress response through regulation of
the adrenal cortex stress hormone, cortisol. Honokiol, a biphenol, is the most important, and well
researched bioactive constituent within the bark of Magnolia. Natura’s Inflam-Away features a
Magnolia bark extract standardized to 50% honokiol concentration. Numerous animal studies have
demonstrated honokiol to act as an anti-stress agent at lower doses, and also as a potent suppressor of
oxidative damage and cancer.
Chinese skullcap (Scutellaria baicalensis)
Scutellaria baicalensis, also known as Baikal skullcap, golden root, or in TCM, “Huang Qin”, is a
member of the mint family grown in China and Russia. It possesses a group of polyphenolic compounds
known as flavonoids, which are extremely potent free-radical scavengers. Baicalein, a major flavonoid
in Chinese skullcap, has shown impressive anti-inflammatory and anti-cancer effects that appear to be
mediated via repression of the 5 and 12-lipoxygenase enzymes, inhibition of interleukin-1B, and
prostaglandin E2. Chinese Skullcap extract also targets several other inflammatory pathways. It inhibits
LPS-induced iNOS and COX-2 gene expression by blocking NF-kB activation.
Chinese skullcap has confirmed anti-arthritic and anti-inflammatory actions, similar in effect to the
prescription drugs phenyl-butazone and indomethacin. Unlike these drugs that are associated with
toxicity and adverse effects, Chinese skullcap does not appear to have any adverse effects at therapeutic
levels.
Andrographis (Andrographis paniculata)
Andrographis is a Chinese herbal medicine well known for its potent anti-cancer, anti-viral, and antibacterial
properties. It is from the family Acanthaceae, and is often referred to as the 'King of Bitters.'
In TCM, this plant is classified as an herb that, “Clears Heat and Cleans Toxins”. It has been used for
millennia for the treatment of infections and cancer. Recent research has uncovered some of the
mechanisms of action responsible for the potent benefits of andrographis.
The most researched active compounds found in Andrographis are its diterpenoids, called
andrographolides. Anrdographolides were found to have anti-inflammatory effects in some in vivo
studies. They reduced inflammation significantly in several animal models, including a model of
induced arthritis. Other animal studies found that andrographolides had analgesic activity, antipyretic
effects, and prevented aspirin-induced ulcers.
The diterpenoids in Andrographis Paniculata (AP) have been shown to induce vasodilation and decrease
heart rate in hypertension. Neoandrographolide, one of the major diterpenoids, is the most potent
compound. The results of one study suggest that vascular smooth muscle is the major site of the
hypotensive effects of andrographis extract. LDH (Lactate dehydrogenase) activity is known to increase
in various cancers due to hypoxic conditions, and it is used as a tumor marker. Another recent study
found a significant decrease in LDH activity on treatment with AP, which indicates a decrease in
carcinogenic activity.
In in-vitro and animal studies, AP extract has been shown to inhibit VEGF (vascular endothelial growth
factor), a growth factor responsible for the development of new vasculature, and a limiting factor for
angiogenesis in tumors. This effect is most likely due to the down-regulation of inflammatory cytokines
responsible for increasing VEGF activity, such as NFk-beta, IL-1 beta, and TIMP-1.
Ginger, bioperine, and bromelain are added for their synergistic effects.
Ginger (Zingiber officinalis)
is a well known harmonizer of digestion, and is often used to balance the ingredients in an herbal
formula. Ginger also influences prostaglandin metabolism and is a potent inhibitor of thromboxane
synthesis, significantly inhibiting platelet aggregation and inflammation.
Bromelain is a well known
enzyme found in pineapples that has powerful protein digesting properties. It is used here to both assist
in the anti-inflammatory effects of the formula, as well as increase the bioavailability of the other
ingredients. Black Pepper (Piper longum) extract has been shown to significantly enhance the bioavailability of various nutrients by prolonging the life of certain herbal constituents, allowing them to be absorbed better and work for longer periods of time. Piperine, a major alkaloid found in pepper has been shown to possess bioavailability-enhancing activity with various structurally and therapeutically diverse herbal compounds.
Quote:
There are two thing to consider when assessing the formula. First and foremost, what is the concentration of Boswellic acids in the extract you are currently taking? As you can see below, the extract we are using contains 30% AKBA, as well as 50% B-Boswellic acids and 75% total acid content. This very high quality and potent extract is patented by Sabinsa.
Second, and much more importantly, is the combination of several other extracts that have a strong effect on the inflammatory cascade, in particular the Andrographis, Feverfew, and Magnolia. These compounds work together synergistically on various parts of this cascade to down regulate inflammation, offering much more activity than Boswellia alone.
J Cancer Res Clin Oncol. 2009 Sep;135(9):1245-55. Epub 2009 Mar 10. Herbal extract "Songyou Yin" inhibits tumor growth and prolongs survival in nude mice bearing human hepatocellular carcinoma xenograft with high metastatic potential.
Huang XY, Wang L, Huang ZL, Zheng Q, Li QS, Tang ZY.
Department of General Surgery, The 6th People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
PURPOSE: Chinese herbs have become a focus of interest in cancer treatment. This study evaluates the effect of the herbal compound extract "Songyou Yin" (containing Salvia miltiorrhiza Bge.-danshen and other four herbs) on hepatocellular carcinoma (HCC). METHODS: Human HCC cell line MHCC97H with high-metastatic potential was employed for in vitro study. In vivo study was conducted in nude mice bearing HCC orthotopic xenograft with MHCC97H. RESULTS: In vitro, "Songyou Yin" caused dramatic attenuation of tumor proliferation by induction of apoptosis that was associated with caspase-3 activation, and inhibit invasiveness of MHCC97H via reducing matrix metalloproteinase-2 (MMP2) activity. In vivo, "Songyou Yin" minimized cancer-related body weight loss of mice bearing tumors without distinct toxicity, and inhibited tumor growth with stepwise increased dosage of "Songyou Yin" and accorded with the expression of proliferating cell nuclear antigen. Moreover, "Songyou Yin" inhibited tumor growth was associated with an increased TUNEL-positive apoptosis as well as a decreased microvessel density and vascular endothelial growth factor (VEGF) abundance, and inhibited tumor invasion via down-regulation of MMP2. The lung metastatic extent was decreased (p < 0.01, compared with control). The life span of nude mice bearing xenografts was 75.0 +/- 3.9 days in "Songyou Yin" group, whereas it was 52.0 +/- 2.3 days in the control (p < 0.001). CONCLUSIONS: Nontoxic herbal compound extract "Songyou Yin" inhibited tumor growth and prolonged survival, via inducing apoptosis and down-regulation of MMP2 and VEGF, which indicated its potential use in patients with advanced HCC.
Chrysin A flavonoid from the Passion Flower that has antioxidant effects
Inhibits 6 of the 7 procancer events
Enhances Tumor Necrosis Factor (TNF) cytotoxicity to cancer cells
Inhibits abnormal hormone action, binds estrogen receptors, alters steroid hormone metabolism, normalizes testosterone and other androgen levels
Inhibits HIV expression and invasion in cell cultures, inhibits HIV-1 transactivation, exhibits anti –HIV activity Coriolus Versicolor
A Chinese herbal mushroom with anticancer effects
Potently stimulates the immune system
Increases the cytotoxicity of natural killer cells
Inhibits the invasion of cancer cells (metastasis and local proliferation)
Inhibits 4 of the 7 procancer events
Increases survival rates in post chemotherapy cancer patients
Provides and anti-viral agent for HIV therapy Diindolymethane (DIM)
DIM is a phytochemical from cruciferous vegetables (broccoli, Brussels sprouts, cabbage)
Provides a strong anti-estrogen effect on cancer cells
Inhibits adhesion, motility, and invasiveness of cancer cells
Inhibits 5 of the 7 procancer events Resveratrol
Non-flavonoid phenolic compound found in grapes
Acts as an antioxidant
Inhibits platelet aggregation and reduces inflammation
Inhibits 6 of the 7 procancer events
Inhibits insulin resistance
Inhibits abnormal estrogen action
Produces anti-HIV activity: inhibits viral replication and proliferation Turmeric Extract (Curcumin)
Acts as a potent antioxidant
Strong anti inflammatory
Inhibits insulin resistance
Inhibits cancer cell proliferation in vitro
Inhibits metastasis in vivo
Inhibits 5 of the 7 procancer events
Inhibits Tat-mediated transactivation of type 1 human immunodeficiency virus long terminal repeat. Tat is a protein secreted by the HIV1-infected cells that may have additional action on the pathogenesis of AIDS Quercetin
A flavonoid that induces cell apoptosis
Strong antioxidant
Strong anti-inflammatory that stabilizes basophils and mast cells
Reduces cholesterol and LDL
Inhibits 6 of the 7 procancer events Green Tea Extract
A flavonoid containing epigallocatechin gallate (EGCG), the primary anticancer agent
Acts as an antioxidant
In-vitro and in-vivo anticancer activity
Inhibits 6 of 7 procancer events
Inhibits activities of HIV-1 transcripts L-Selenium Methionine
The organic form of selenium, which is better utilized by the body
Acts as an antioxidant
Inhibits 6 of the 7 procancer events
In-vitro and in-vivo studies show anticancer effects
Strong immune stimulator
Helps restore plasma selenium levels that are low in cancer and HIV patients Other Ingredients: Water, Liposomal Matrix (Lecithin Complex with Phosphadidyl Choline and Phosphatidylserine), Natural Flavors, Stevia, Sodium Benzoate and Potassium Sorbate (as preservatives) SYNERGISM
Synergism benefits cancer therapy resulting in lower dosages of drugs or compounds. Many natural compounds need synergism with other compounds to be effective against cancer, HIV, and other immunodeficiency diseases. It is best to use several natural compounds together in a mixture to enhance the synergetic action of each compound. LIPOSOMAL DELIVERY SYSTEM
The unique property of a liposomal delivery system is a higher cellular uptake and a prolonged circulation of therapeutic agents. Use of a liposomal delivery system is essential to maximize the actions of natural compounds. CONCLUSION
It is apparent in reviewing the research that the proper mixture of natural compounds applied at a therapeutic level, combined with the appropriate delivery system, can effectively allow your body to reverse the destructive capacities of cancer, HIV, and other immunodeficiency diseases.
Liposomal CAN-HELP Support Formula is designed to provide nutritional support for the cancer patient. It is not being sold as a cure for cancer. It is formulated with the knowledge of the vast amount of research which has been accomplished on enhancing the body’s ability to fight and overcome cancer through the use of the following anti-cancer nutrients.
The ingredients of this special liquid formula are:
These five ingredients are blended in a proprietary formula based on NanoLiposomal delivery which creates a possibility of benefit never before experienced in a single formula. Most will feel these benefits within the first week and they will continue as long as you consume the formula.
Cancer is a terrible disease, devastating to the patient and to all those around him or her. The law says you can only treat cancer with surgery, radiation or chemotherapy. This does not curtail the patient or those who would help, to supply supplements that have been proven to make their body stronger and more capable of tolerating these insults to the body. Many ingredients of this formula have hundreds of research papers written about them illustrating that the outcome in cancer was infinitely more beneficial if this or that nutrient were used. Liposomal CAN-HELP is an attempt to bring as many of these ingredients together in a simple-to-take supplemental form for those who feel they need support.
CLICK ON THE LINKS BELOW TO LEARN MORE ABOUT THE NUTRIENTS CONTAINED IN THE
LIPOSOMAL CAN-HELP FORMULA:
BMC Cancer. 2010 Apr 30;10(1):175. [Epub ahead of print] Inhibition of metastasis, angiogenesis, and tumor growth by Chinese herbal cocktail Tien-Hsien Liquid.
ABSTRACT: BACKGROUND: Advanced cancer is a multifactorial disease that demands treatments targeting multiple cellular pathways. Chinese herbal cocktail which contains various phytochemicals may target multiple dys-regulated pathways in cancer cells and thus may provide an alternative/complementary way to treat cancers. Previously we reported that the Chinese herbal cocktail Tien-Hsien Liguid (THL) can specifically induce apoptosis in various cancer cells and have immuno-modulating activity. In this study, we further evaluated the anti-metastatic, anti-angiogenic and anti-tumor activities of THL with a series of in vitro and in vivo experiments. METHODS: The migration and invasion of cancer cells and endothelial cells was determined by Boyden chamber transwell assays. The effect of THL on pulmonary metastasis was done by injecting CT-26 colon cancer cells intravenously to syngenic mice. The in vitro and in vivo microvessel formation was determined by the tube formation assay and the Matrigel plug assay, respectively. The in vivo anti-tumor effect of THL was determined by a human MDA-MB-231 breast cancer xenograft model. The expression of metalloproteinase (MMP)-2, MMP-9, and urokinase plasminogen activator (uPA) was measured by gelatin zymography. The expression of HIF-1 alpha and the phosphorylation of ERK1/2 were determined by Western blot. RESULTS: THL inhibited the migration and invasion ability of various cancer cells in vitro, decreased the secretion of MMP-2, MMP-9, and uPA and the activity of ERK1/2 in cancer cells, and suppressed pulmonary metastasis of CT-26 cancer cells in syngenic mice. Moreover, THL inhibited the migration, invasion, and tube formation of endothelial cells in vitro, decreased the secretion of MMP-2 and uPA in endothelial cells, and suppressed neovascularization in Matrigel plugs in mice. Besides its inhibitory effect on endothelial cells, THL inhibited hypoxia-induced HIF-1 alpha and vascular endothelial growth factor-A expression in cancer cells. Finally, our results show that THL inhibited the growth of human MDA-MB-231 breast cancer xenografts in NOD-SCID mice. This suppression of tumor growth was associated with decreased microvessel formation and increased apoptosis caused by THL. CONCLUSION: Our data demonstrate that THL had broad-spectra anti-cancer activities and merits further evaluation for its use in cancer therapy.
PMID: 20429953 [PubMed - as supplied by publisher]Free Article
Carcinogenesis. 2006 Dec;27(12):2455-63. Epub 2006 Jun 15. An oriental herbal cocktail, ka-mi-kae-kyuk-tang, exerts anti-cancer activities by targeting angiogenesis, apoptosis and metastasis.
Lee HJ, Lee EO, Rhee YH, Ahn KS, Li GX, Jiang C, Lü J, Kim SH.
Laboratory of Angiogenesis and Chemoprevention, College of Oriental Medicine, Kyunghee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 131-701, Republic of Korea.
Rigorous and systematic pre-clinical studies are necessary and essential to establish the efficacy and safety of Oriental herbs and formulas in order to transform traditional herbal practices into evidence-based medicine. Here we evaluated the anti-cancer activities of the ethanol extract of Ka-mi-kae-kyuk-tang (KMKKT), a formula of ten Oriental herbs, with a battery of in vitro and in vivo mechanism-based biomarkers involving angiogenesis, apoptosis and metastasis. The results show that KMKKT suppressed the vascular endothelial responses by inhibiting basic fibroblast growth factor (bFGF)-induced ERK1/2 phosphorylation, cell migration as well as tube formation in the human umbilical vein endothelial cell model, and decreased the hypoxia-induced HIF1alpha and vascular epithelial growth factor (VEGF) expression in the mouse Lewis lung carcinoma (LLC) cells in vitro, and inhibited the bFGF-induced angiogenesis in chick chorioallantoic membrane model, and in the Matrigel plugs in mice. Intraperitoneal delivery of KMKKT potently inhibited the growth of the subcutaneously inoculated LLC cells in syngenic mice. In addition, KMKKT inhibited the invasion ability of the mouse colon 26-L5 cancer cells in vitro and decreased their formation of liver metastasis when intraportally inoculated in syngenic mice. Furthermore, KMKKT suppressed the growth of the human PC-3 prostate cancer xenografts in athymic nude mice and averted the cancer-related body weight loss. The in vivo cancer growth suppression was associated with a decreased microvessel density and VEGF abundance as well as an increased PARP cleavage and the TUNEL-positive apoptosis. Together, our data support broad-spectra in vivo anti-cancer activities of KMKKT targeting angiogenesis, apoptosis and metastasis without any adverse effect on the body weight. This formula merits serious consideration for further evaluation for the chemoprevention and treatment of cancers of multiple organ sites.
PMID: 16777983 [PubMed - indexed for MEDLINE]Free Article
Dx'd w/multifocal DCIS/IDS 3/08
7mm invasive component
Partial mast. 5/08
Stage 1b, ER 80%, PR 90%, HER-2 6.9 on FISH
0/5 nodes
4 AC, 4 TH finished 9/08
Herceptin every 3 weeks. Finished 7/09
Tamoxifen 10/08. Switched to Femara 8/09
Bilat SPM w/reconstruction 10/08
Clinical Trial w/Clondronate 12/08
Stopped Clondronate--too hard on my gizzard!
Switched back to Tamoxifen due to tendon pain from Femara
15 Years NED
I think I just might hang around awhile....
Curcumin Concentrate: One can go on and on about this ancient herb which has stood the test of time over and over again. Scientists marvel at the adaptogenic properties (ability to normalize) that curcumin offers the user. One of those is the ability to reduce inflammation. Hundreds of research papers authenticate this function – even to the point of doing a head-on test with steroids – and curcumin won! People use it all the time for this purpose.
It is now clear that many health concerns are related by the presence of inflammation. If you relieve inflammation you can relieve pain. Researchers have discovered an all-natural combination of ingredients that will support the body’s healthy inflammation response.
We know that pain is the result of inflammation, so it makes sense that if you can reduce the inflammation, you can reduce pain. The real plus is that you do this naturally – without side effects!
Boswellia is an herb that has come to the fore in recent times as another anti-inflammatory herb. Boswellia, although not quite up to curcumin, works synergistically to naturally reduce inflammation.. They make a great duo.
Green Tea was used for years in Asia, but now, everyone has learned of the many benefits to the human body of this beverage. EGCG is the catechin contained in green tea that produces a remarkable change in the cellular structure of the body. An effective free radical fighter and cellular detoxifier, green tea is an excellent addition to your diet.
Cetyl Myristoleate (CMO) is an ingredient belonging to the fatty acid group. CMO has multiple biological properties, including as an anti-inflammatory and a pain reliever, as well as being an immune system modulator. Not known to many but used successfully by others, CMO contributes much to this combination.
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