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Planta Med 2008; 74(1): 39-42
DOI: 10.1055/s-2007-993779
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Berberine Inhibits Growth of the Breast Cancer Cell Lines MCF-7 and MDA-MB-231

Jong Bin Kim2 , Kyung-Min Lee2 , Eunyoung Ko1 , Wonshik Han1 , Jeong Eon Lee1 , Incheol Shin4 , Ji-Yeon Bae2 , Sangmin Kim3 , Dong-Young Noh1 , 2
  • 1Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
  • 2Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
  • 3Clinical Research Institute, Seoul National University College of Medicine, Seoul, Korea
  • 4Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Korea
Further Information

Publication History

Received: October 19, 2007 Revised: November 25, 2007

Accepted: November 27, 2007

Publication Date:
17 January 2008 (online)

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Abstract

The effects of berberine on the behavior of breast tumors have not yet been established. To determine whether this compound is useful in the treatment of breast cancer, we analyzed the impact of berberine on the human breast cancer cell lines MCF-7 and MDA-MB-231 cells. Berberine was added to proliferating MCF-7 and MDA-MB-231 cells in culture. Following treatment, changes in cell growth characteristics such as proliferation, cell cycle duration, and the degree of apoptosis were assayed. Following berberine treatment, a time-dependent reduction in proliferation was observed in both cell lines at differing concentrations: 20 μM for MCF-7 and 10 μM for MDA-MB-231 cells. Annexin V staining showed an increase in apoptosis in both cell lines of 31 % in MCF-7and 12 % in MDA-MB-231 cells compared to their respective controls. In addition, 12 % of the MCF-7 cells were arrested at G0/G1, compared to 62 % of control cells. These results demonstrate that treatment with berberine inhibits growth in both MDA-MB-231 and MCF-7 cells. In addition, they show that this partly occurs through the induction of apoptosis in MDA-MB-231 cells, and through both cell cycle arrest and induction of apoptosis in MCF-7 cells. Thus, berberine may be a novel therapeutic drug for breast cancer.

Key words

Berberine - breast cancer - MCF-7 - MDA-MB-231 - apoptosis

References

  • 1 Jantova S, Cipak L, Cernakova M, Kost'alova D. Effect of berberine on proliferation, cell cycle and apoptosis in HeLa and L1210 cells.  J Pharm Pharmacol. 2003;  55 1143-9
    CrossrefPubMedGoogle Scholar
  • 2 Lee S, Lim H J, Park H Y, Lee K S, Park J H, Jang Y. Berberine inhibits rat vascular smooth muscle cell proliferation and migration in vitro and improves neointima formation after balloon injury in vivo. Berberine improves neointima formation in a rat model.  Atherosclerosis. 2006;  186 29-37
    CrossrefPubMedGoogle Scholar
  • 3 Abidi P, Zhou Y, Jiang J D, Liu J. Extracellular signal-regulated kinase-dependent stabilization of hepatic low-density lipoprotein receptor mRNA by herbal medicine berberine.  Arterioscler Thromb Vasc Biol. 2005;  25 2170-6
    CrossrefPubMedGoogle Scholar
  • 4 Issat T, Jakobisiak M, Golab J. Berberine, a natural cholesterol reducing product, exerts antitumor cytostatic/cytotoxic effects independently from the mevalonate pathway.  Oncol Rep. 2006;  16 1273-6
    PubMedGoogle Scholar
  • 5 Kuo C L, Chi C W, Liu T Y. Modulation of apoptosis by berberine through inhibition of cyclooxygenase-2 and Mcl-1 expression in oral cancer cells.  In Vivo. 2005;  19 247-52
    PubMedGoogle Scholar
  • 6 Leng S H, Lu F E, Xu L J. Therapeutic effects of berberine in impaired glucose tolerance rats and its influence on insulin secretion.  Acta Pharmacol Sin. 2004;  25 496-502
    PubMedGoogle Scholar
  • 7 Jantova S, Letasiova S, Brezova V, Cipak L, Labaj J. Photochemical and phototoxic activity of berberine on murine fibroblast NIH-3T3 and Ehrlich ascites carcinoma cells.  J Photochem Photobiol B. 2006;  85 163-76
    CrossrefPubMedGoogle Scholar
  • 8 Inoue K, Kulsum U, Chowdhury S A, Fujisawa S, Ishihara M, Yokoe I. et al . Tumor-specific cytotoxicity and apoptosis-inducing activity of berberines.  Anticancer Res. 2005;  25 4053-9
    PubMedGoogle Scholar
  • 9 Mantena S K, Sharma S D, Katiyar S K. Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP.  Carcinogenesis. 2006;  27 2018-27
    CrossrefPubMedGoogle Scholar
  • 10 Lin C C, Kao S T, Chen G W, Ho H C, Chung J G. Apoptosis of human leukemia HL 60 cells and murine leukemia WEHI-3 cells induced by berberine through the activation of caspase-3.  Anticancer Res. 2006;  26 227-42
    PubMedGoogle Scholar
  • 11 Letasiova S, Jantova S, Miko M, Ovadekova R, Horvathova M. Effect of berberine on proliferation, biosynthesis of macromolecules, cell cycle and induction of intercalation with DNA, dsDNA damage and apoptosis in Ehrlich ascites carcinoma cells.  J Pharm Pharmacol. 2006;  58 263-70
    CrossrefPubMedGoogle Scholar
  • 12 Peng P L, Hsieh Y S, Wang C J, Hsu J L, Chou F P. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase plasminogen activator and matrix metalloproteinase-2.  Toxicol Appl Pharmacol . 2006;  214 8-15
    CrossrefPubMedGoogle Scholar
  • 13 Orfila L, Rodriguez M, Colman T, Hasegawa M, Merentes E, Arvelo F. Structural modification of berberine alkaloids in relation to cytotoxic activity in vitro. .  J Ethnopharmacol. 2000;  71 449-56
    CrossrefPubMedGoogle Scholar
  • 14 Lin J G, Chung J G, Wu L T, Chen G W, Chang H L, Wang T F. Effects of berberine on arylamine N-acetyltransferase activity in human colon tumor cells.  Am J Chin Med. 1999;  27 265-75
    PubMedGoogle Scholar
  • 15 Kang M R, Chung I K. Down-regulation of DNA topoisomerase IIalpha in human colorectal carcinoma cells resistant to a protoberberine alkaloid, berberrubine.  Mol Pharmacol. 2002;  61 879-84
    CrossrefPubMedGoogle Scholar
  • 16 Kim S A, Kwon Y, Kim J H, Muller M T, Chung I K. Induction of topoisomerase II mediated DNA cleavage by a protoberberine alkaloid, berberrubine.  Biochemistry. 1998;  37 16 316-24
    PubMedGoogle Scholar
  • 17 Wu S N, Yu H S, Jan C R, Li H F, Yu C L. Inhibitory effects of berberine on voltage- and calcium-activated potassium currents in human myeloma cells.  Life Sci. 1998;  62 2283-94
    CrossrefPubMedGoogle Scholar
  • 18 Sheridan C, Kishimoto H, Fuchs R K, Mehrotra S, Bhat-Nakshatri P, Turner C H. et al . CD44+/CD24-breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis.  Breast Cancer Res. 2006;  8 R59
    CrossrefPubMedGoogle Scholar
  • 19 Lin C C, Lin S Y, Chung J G, Lin J P, Chen G W, Kao S T. Down-regulation of cyclin B1 and up-regulation of Wee1 by berberine promotes entry of leukemia cells into the G2/M-phase of the cell cycle.  Anticancer Res. 2006;  26 1097-104
    PubMedGoogle Scholar

Dong-Young Noh, M.D., Ph. D.

Cancer Research Institute and Department of Surgery

Seoul National University College of Medicine

28 Yongon-dong

Chongno-gu

Seoul 110-744

Korea

Phone: +82-2-760-2921

Fax: +82-2-766-3975

Email: dynoh@snu.ac.kr

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