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.
LINK
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.
PDF brochure
http://www.naturalhealthyconcepts.co...-products.html
2 capsules=(in mg)
Boswellin ® Super (Sabinsa)
| 30% AKBA / 50% B-Boswellic acid / 75% total acids
| |
Feverfew Extract
| .8 % parthenolide
| |
Magnolia Extract
| 50% Honokiol
| |
Andrographis
| 50% Andrographolides
| |
Chinese Skullcap 8:1
|
| |
Ginger (Sabinsa)
| 5% gingerols
| |
Bromelain
| 2400 GDU
| |
Bioperine®
| 95% Piperine
| |
|
| |
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.
PMID: 19277711 [PubMed - indexed for MEDLINE]
http://www.lifeone.org/therapies_cancer.html
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.
http://www.healthyitems.com/Liposoma...HELP-p/601.htm
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:
Liposomal Glutathione
Liposomal Resveratrol
Liposomal Curcumin
Liposomal CoQ10
Liposomal Vitamin C
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:
XYMOGEN professional supplements: http://www.xymogen.com/2008/index.asp
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.
Chia JS,
Du JL,
Hsu WB,
Sun A,
Chiang CP,
Wang WB.
FREE TEXT
Abstract
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.
FREE TEXT
Abstract
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