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Old 04-05-2010, 09:46 PM   #1
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Anticancer Drugs. 2009 Oct;20(9):757-69.
A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs.

Sun Y, Xun K, Wang Y, Chen X.
School of Pharmacy, Chengdu Medical College, Chengdu, China.
Natural products represent a rich reservoir of potential small chemical molecules exhibiting antiproliferation and anticancer properties. An example is berberine, a protoberberine alkaloid widely distributed in medical plants used in traditional Chinese prescriptions. Recent advances have shown that berberine exerts anticancer activities both in vitro and in vivo through different mechanisms. Berberine shows inhibitory effects on the proliferation and reproduction of certain tumorigenic microorganisms and viruses, such as Heliobacter pylori and hepatitis B virus. Transcriptional regulation of some oncogene and carcinogenesis-related gene expression and interaction with both DNA and RNA are also well documented. Besides, berberine is a broad spectrum enzyme inhibitor, which affects N-acetyltransferase, cyclooxygenase-2, and topoisomerase activities and gene/protein expression. These actions, together with the regulation of reactive oxygen species production, mitochondrial transmembrane potential, and nuclear factor-kappaB activation might underlie its antiproliferative and proapoptotic effects. More importantly, the suppression of tumor growth and metastasis, the beneficial application in combined medication, and the improvement of multidrug resistance both in vivo and in vitro clearly show its potential as an alternative medicine for tumor chemotherapy.

PMID: 19704371 [PubMed - indexed for MEDLINE]

Phytomedicine. 2009 Oct 1. [Epub ahead of print]
The alkaloid Berberine inhibits the growth of Anoikis-resistant MCF-7 and MDA-MB-231 breast cancer cell lines by inducing cell cycle arrest.

Kim JB, Yu JH, Ko E, Lee KW, Song AK, Park SY, Shin I, Han W, Noh DY.
Cancer Research Institute, Seoul National University College of Medicine, 28 Yeongeon-dong, Jongno-gu, Seoul 110-799, Republic of Korea.
Berberine is a pure phenanthren alkaloid isolated from the roots and bark of herbal plants such as Berberis, Hydrastis canadensis and Coptis chinensis. Berberine has been established to inhibit the growth of breast cancer cells, but its effects on the drug resistance and anoikis-resistance of breast cancer cells have yet to be elucidated. Anoikis, or detachment-induced apoptosis, may prevent cancer progression and metastasis by blocking signals necessary for survival of localized cancer cells. Resistance to anoikis is regarded as a prerequisite for metastasis; however, little is known about the role of berberine in anoikis-resistance. We established anoikis-resistant cells from the breast cancer cell lines MCF-7 and MDA-MB-231 by culturing them on a Poly-Hema substratum. We then investigated the effects of berberine on the growth of these cells. The anoikis-resistant cells had a reduced growth rate and were more invasive than their respective adherent cell lines. The effect of berberine on growth was compared to that of doxorubicine, which is a drug commonly used to treat breast cancer, in both the adherent and anoikis-resistant cell lines. Berberine promoted the growth inhibition of anoikis-resistant cells to a greater extent than doxorubicine treatment. Treatment with berberine-induced cell cycle arrest at G0/G1 in the anoikis-resistant MCF-7 and MDA-MB-231 cells as compared to untreated control cells. In summary, these results revealed that berberine can efficiently inhibit growth by inducing cell cycle arrest in anoikis-resistant MCF-7 and MDA-MB-231 cells. Further analysis of these phenotypes is essential for understanding the effect of berberine on anoikis-resistant breast cancer cells, which would be relevant for the therapeutic targeting of breast cancer metastasis.

PMID: 19800775 [PubMed - as supplied by publisher]

Asian Pac J Cancer Prev. 2007 Jul-Sep;8(3):390-4.
Effect of homeopathic medicines on transplanted tumors in mice.


Es S, Kuttan G, Kc P, Kuttan R.
Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala State, India. 680555.
Ultra low doses used in homeopathic medicines are reported to have healing potential for various diseases but their action remains controversial. In this study we have investigated the antitumour and antimetastatic activity of selected homeopathic medicines against transplanted tumours in mice. It was found that Ruta graveolens 200c and Hydrastis canadensis 200c significantly increased the lifespan of Ehrlich Ascites Carcinoma and Dalton's Lymphoma Ascites induced tumour-bearing animals by 49.7%, and 69.4% respectively. Moreover there was 95.6% and 95.8% reduction of solid tumour volume in Ruta 200c and Hydrastis 200c treated animals on the 31st day after tumour inoculation. Hydrastis 1M given orally significantly inhibited the growth of developed solid tumours produced by DLA cells and increased the lifespan of tumour bearing animals. Some 9 out of 15 animals with developed tumors were completely tumour free after treatment with Hydrastis 1M. Significant anti-metastatic activity was also found in B16F-10 melanoma-bearing animals treated with Thuja1M, Hydrastis 1M and Lycopodium1M. This was evident from the inhibition of lung tumour nodule formation, morphological and histopathological analysis of lung and decreased levels of gamma-GT in serum, a cellular marker of proliferation. These findings support that homeopathic preparations of Ruta and Hydrastis have significant antitumour activity. The mechanism of action of these medicines is not known at present.

PMID: 18159975 [PubMed - indexed for MEDLINE]

Biochem Biophys Res Commun. 2009 Jan 9;378(2):174-8. Epub 2008 Nov 8.
Coptis extracts enhance the anticancer effect of estrogen receptor antagonists on human breast cancer cells.

Liu J, He C, Zhou K, Wang J, Kang JX.
Departmement of Medicine, Massachusetts General Hospital and Harvard Medical School, 149 - 13th Street, Room 4433, Charlestown, MA 02129, USA.
Estrogen receptor (ER) antagonists have been widely used for breast cancer treatment, but the efficacy and drug resistance remain to be clinical concerns. The purpose of this study was to determine whether the extracts of coptis, an anti-inflammatory herb, improve the anticancer efficacy of ER antagonists. The results showed that the combined treatment of ER antagonists and the crude extract of coptis or its purified compound berberine conferred synergistic growth inhibitory effect on MCF-7 cells (ER+), but not on MDA-MB-231 cells (ER-). Similar results were observed in the combined treatment of fulvestrant, a specific aromatase antagonist. Analysis of the expression of breast cancer related genes indicated that EGFR, HER2, bcl-2, and COX-2 were significantly downregulated, while IFN-beta and p21 were remarkably upregulated by berberine. Our results suggest that coptis extracts could be promising adjuvant to ER antagonists in ER positive breast cancer treatment through regulating expression of multiple genes.

PMID: 19000652 [PubMed - indexed for MEDLINE]

J Cell Biochem. 2010 Sep 9. [Epub ahead of print]
Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: the cellular mechanism.

Wang N, Feng Y, Zhu M, Tsang CM, Man K, Tong Y, Tsao SW.
School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, PR of China.



Extensive studies have revealed that berberine, a small molecule derived from Coptidis Rhizoma (Huanglian in Chinese) and many other plants, has strong anti-tumor properties. To better understand berberine-induced cell death and its underlying mechanisms in cancer, we examined autophagy and apoptosis in the human hepatic carcinoma cell lines HepG2 and MHCC97-L. The results of this study indicate that berberine can induce both autophagy and apoptosis in hepatocellular carcinoma cells. Berberine-induced cell death in human hepatic carcinoma cells was diminished in the presence of the cell death inhibitor 3-Methyladenine, or following interference with the essential autophagy gene Atg5. Mechanistic studies showed that berberine may activate mitochondrial apoptosis in HepG2 and MHCC97-L cells by increasing Bax expression, the formation of permeable transition pores, cytochrome C release to cytosol, and subsequent activation of the caspase-3 and caspase-9 execution pathway. Berberine may also induce autophagic cell death in HepG2 and MHCC97-L cells through activation of Beclin-1 and inhibition of the mTOR signaling pathway by suppressing the activity of Akt and up-regulating P38 MAPK signaling. This is the first study to describe the role of Beclin-1 activation and mTOR inhibition in berberine-induced autophagic cell death. These results further demonstrate the potential of berberine as a therapeutic agent in the emerging list of cancer therapies with novel mechanisms. © 2010 Wiley-Liss, Inc.

PMID: 20830746 [PubMed - as supplied by publisher]

Diabetes. 2006 Aug;55(8):2256-64.
Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states.


Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, Lee CH, Oh WK, Kim CT, Hohnen-Behrens C, Gosby A, Kraegen EW, James DE, Kim JB.
Department of Biological Sciences, Seoul National University, San 56-1, Sillim-Dong, Kwanak-Gu, Korea. E-mail: jaebkim@snu.ac.kr d.james@garvan.org.au

Berberine has been shown to have antidiabetic properties, although its mode of action is not known. Here, we have investigated the metabolic effects of berberine in two animal models of insulin resistance and in insulin-responsive cell lines. Berberine reduced body weight and caused a significant improvement in glucose tolerance without altering food intake in db/db mice. Similarly, berberine reduced body weight and plasma triglycerides and improved insulin action in high-fat-fed Wistar rats. Berberine downregulated the expression of genes involved in lipogenesis and upregulated those involved in energy expenditure in adipose tissue and muscle. Berberine treatment resulted in increased AMP-activated protein kinase (AMPK) activity in 3T3-L1 adipocytes and L6 myotubes, increased GLUT4 translocation in L6 cells in a phosphatidylinositol 3' kinase-independent manner, and reduced lipid accumulation in 3T3-L1 adipocytes. These findings suggest that berberine displays beneficial effects in the treatment of diabetes and obesity at least in part via stimulation of AMPK activity.

PMID: 16873688 [PubMed - indexed for MEDLINE]

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005 Dec;149(2):461-3.
Antiproliferative activity of berberine in vitro and in vivo.


Letasiová S, Jantová S, Múcková M, Theiszová M.
Department of Biochemistry and Microbiology, Slovak University of Technology, Radlinského 9, Bratislava, Slovak Republic. silvia.letasiova@stuba.sk
Berberine, an isoquinoline plant alkaloid acted cytotoxically in vitro on tumour cell lines B16. Its anticancer activity in vivo was studied with the transplanted B16 line in the range of doses from 1 mg/kg to 10 mg/kg. The significant reduction of tumor volume was observed on day 16 at doses of 5 and 10 mg/kg. The dose of 1 mg/kg stimulated the tumor mass, but other tested concentration, 5 and 10 mg/kg, reduced the tumor weight.

PMID: 16601810 [PubMed - indexed for MEDLINE]


Berberine benefit, side effects, by Ray Sahelian, M.D. Benefit of berberine supplement hydrochloride sulfate hcl
Role in diabetes, cholesterol and other medical conditions
Berberine is a plant alkaloid isolated from the roots and bark of several herbs. Some of these herbs include:

Barberry (Berberis vulgaris), Berberis integerrima. Berbamine and berberine are found in the plant barberry.
Coptis chinensis or Berberis aristata
Goldenseal (Hydrastis canadensis)
Oregon Grape (Berberis aquifolium)
Phellodendron Amurense
Yerba mansa (Anemopsis californica).

The berberine alkaloid can be found in the roots, rhizomes, stem, and bark of the plants. Berberine-containing plants are used medicinally in many traditional medical systems, including Ayurvedic herbal and Chinese herbal medicine.
Coptis chinensis rhizome -- Golden Thread -- Huang Lian -- Intense yellow color most likely due to high content of berberine, which is very bitter in taste.
Berberine potential benefits
Some people claim berberine is useful for fungal, candida, yeast, parasites, bacterial and viral infections. Berberine extracts and decoctions have demonstrated antimicrobial activity against a variety of organisms including bacteria, viruses, fungi, protozoans, helminths, and chlamydia. Currently, the predominant clinical uses of berberine include bacterial diarrhea, intestinal parasite infections, and ocular trachoma infections.
Berberine has been tested in diabetes, prostate cancer, cardiac arrhythmia and leukemia.

Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):529-42.
Synergistic tumor-killing effect of radiation and berberine combined treatment in lung cancer: the contribution of autophagic cell death.

Peng PL, Kuo WH, Tseng HC, Chou FP.
Institute of Biochemistry and Biotechnology, College of Medicine, Chung Shan Medical University, Taichung, Taiwan.
PURPOSE: Radiotherapy is the most efficacious strategies for lung cancer. The radiation-enhancing effects and the underlying mechanisms of berberine were investigated both in vitro and in vivo. METHODS AND MATERIALS: Clonogenic survival assays were used to evaluate the radio-sensitivity of berberine on non-small-cell lung cancer. Electron microscopic observation of the features of cell death, flow cytometry of acidic vascular organelles formation, mitochondria membrane potential and cell-cycle progression, and Western blotting of caspase 3, PARP, and LC3 were performed to identify the mechanisms underlying the enhancing effects. Lewis lung carcinoma model in mice was conducted to evaluate the possible application of berberine in synergistic treatment with irradiation. RESULTS: Compared with radiation alone (SF2 = 0.423; D(0) = 5.29 Gy), berberine at 5 and 10 muM concentrations in combination with radiation showed significant enhancement on radiation-induced clonogenic inhibition (SF2 = 0.215: D(0) = 2.70 Gy and SF2 = 0.099: D(0) = 1.24 Gy) on A549 cells. The cellular ultrastructure showed the presence of autophagosome and an increased proportion of acridine orange stain-positive cells, demonstrating that berberine enhanced radiosensitivity via autophagy. The process involved LC3 modification and mitochondrial disruption. The animal model verified the synergistic cytotoxic effect of berberine and irradiation resulting in a substantial shrinkage of tumor volume. CONCLUSION: Supplement of berberine enhanced the cytotoxicity of radiation in both in vivo and in vitro models of lung cancer. The mechanisms underlying this synergistic effect involved the induction of autophagy. It suggests that berberine could be used as adjuvant therapy to treat lung cancer.

PMID: 18207031 [PubMed - indexed for MEDLINE]

Cancer Chemother Pharmacol. 2008 May;61(6):1007-18. Epub 2007 Jul 28.
Different concentrations of berberine result in distinct cellular localization patterns and cell cycle effects in a melanoma cell line.

Serafim TL, Oliveira PJ, Sardao VA, Perkins E, Parke D, Holy J.
Center of Neurosciences and Cellular Biology, Department of Zoology, University of Coimbra, P3004-597 Coimbra, Portugal.
PURPOSE: Natural products represent a rich reservoir of potential small molecule inhibitors exhibiting antiproliferative and tumoricidal properties. An example is the isoquinoline alkaloid berberine, which is found in plants such as goldenseal (Hydrastis canadensis). Studies have shown that berberine is able to trigger apoptosis in different malignant cell lines, and can also lead to cell cycle arrest at sub-apoptotic doses. A particularly interesting feature of berberine is the fact that it is a fluorescent molecule, and its uptake and distribution in cells can be studied by flow cytometry and epifluorescence microscopy. To test the relationships between berberine uptake, distribution and cellular effect in melanoma cells, K1735-M2 mouse and WM793 human melanoma cells were treated with different concentrations of berberine, and alterations in cell cycle progression, DNA synthesis, cell proliferation, and cell death measured. METHODS: Cell proliferation was measured by sulforhodamine B assays, cell death by flow cytometry, berberine uptake and distribution by laser scanning confocal microscopy and flow cytometry, cell cycle progression by flow cytometry, and DNA synthesis, M-phase, and mitochondrial effects by immunolabeling and epifluorescence microscopy methods. RESULTS: In these melanoma cell lines, berberine at low doses (12.5-50 muM) is concentrated in mitochondria and promotes G1 arrest. In contrast, higher doses (over 50 muM) result in cytoplasmic and nuclear berberine accumulation, and G2 arrest. DNA synthesis is not markedly affected by low doses of berberine, but 100 muM is strongly inhibitory. Even at 100 muM, berberine inhibits cell growth with relatively little induction of apoptosis. CONCLUSION: Berberine displays multiphasic effects in these malignant cell lines, which are correlated with the concentration and intracellular distribution of this alkaloid. These results help explain some of the conflicting information in the literature regarding the effects of berberine, and suggest that its use in clinical development may be more as a cytostatic agent than a cytotoxic compound.

PMID: 17661039 [PubMed - indexed for MEDLINE]

Mol Pharmacol. 2004 Sep;66(3):612-9.
Berberine inhibits HIF-1alpha expression via enhanced proteolysis.


Lin S, Tsai SC, Lee CC, Wang BW, Liou JY, Shyu KG.
Department of Medical Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wen Chang Road, Shih Lin, Taipei 111, Taiwan, Republic of China.
We have studied the antiangiogenic property of berberine. We showed that berberine could directly inhibit in vitro human umbilical vein endothelial cell (HUVEC) tube formation and migration. In addition, to determine whether berberine could influence the cross-talk between the gastric adenocarcinoma cell line SC-M1 and vascular endothelial cells, we performed modified confrontation culture experiments and showed that berberine (7.5 microM, 16 h) could inhibit the capacity of hypoxic SC-M1 cells to stimulate HUVEC migration. These results demonstrated berberine's antiangiogenic property and its clinical potential as an inhibitor of tumor angiogenesis. Parallel Western blot analyses revealed that berberine prevented hypoxic SC-M1 cultures from expressing vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha, two key factors in mediating tumor angiogenesis. However, overexpression of HIF-1alpha in SC-M1 cells dramatically reversed the inhibitory effect of berberine on SC-M1-induced in vitro HUVEC migration. These data indicated that HIF-1alpha repression is a critical step in the inhibitory effect of berberine on tumor-induced angiogenesis. Northern blot analyses plus pulse-chase assays revealed that berberine did not down-regulate HIF-1alpha mRNA but destabilized HIF-1alpha protein. We found that berberine-induced HIF-1alpha degradation was blocked by a 26S proteasome inhibitor. Moreover, immunoprecipitation and Western blot analyses showed that berberine increased the lysine-acetylated HIF-1alpha in hypoxic SC-M1 cultures. These data indicated that a proteasomal proteolytic pathway and lysine acetylation were involved in berberine-triggered HIF-1alpha degradation. In conclusion, our data provided molecular evidence to support berberine as a potent antiangiogenic agent in cancer therapy.

PMID: 15322253 [PubMed - indexed for MEDLINE]

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Old 04-06-2010, 02:38 AM   #2
Ellie F
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Re: Berberine/goldenseal

Can you enlighten me as to which of the cells tested are her 2 positive??Thought it was MCF-7 but can't remember what Lani said in previous post
Thanks Ellie
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Old 04-06-2010, 10:22 AM   #3
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Re: Berberine/goldenseal/Coptis

I don't think either are Her2 positive. MCF7 is ER+, MDA-MB-231 is ER-


Added an abstract showing EGFR and HER2 are downregulated by Berberine/Coptis

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Old 09-12-2010, 01:51 PM   #4
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Re: Berberine/goldenseal

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