ABCR  Vol.3 No.3 , July 2014
Study of the Effect of Silymarin on Viability of Breast Cancer Cell Lines
Abstract: Background: Breast cancer is the most prevalent cancer and results in 14% of cancer-related deaths among women worldwide. The aim of this study is to investigate the anticancer effects of Silymarin on two breast cancer cell lines (BT-474, SK-BR-3). Methods and Material: Two breast cancer cell lines—SK-BR-3 and BT-474—were incubated for 24 hours in standard conditions before adding 100, 200, 400, 800, 1600 μM Silymarin to each well. Alamar blue was then added to the wells after 24, 48 and 72 hours of incubation and cell viability was determined using fluorescence reader to detect the optical density. Results were analyzed using generalized estimating equations (GEE) method in STATA 12.0. Results: we demonstrated the Silybum marianum inhibition of two-cell lines SK-BR-3 and BT-474 growth at different concentrations after 24, 48 and 72 hours. Silymarin increased cell death in both cell lines. Conclusion: Silymarin can be combined with other anti-neoplastic agents to obtain better results.
Cite this paper: Hajighasemlou, S. , Farajollahi, M. , Alebouyeh, M. , Rastegar, H. , Manzari, M. , Mirmoghtadaei, M. , Moayedi, B. , Ahmadzadeh, M. , Kazemi, M. , Parvizpour, F. and Gharibzadeh, S. (2014) Study of the Effect of Silymarin on Viability of Breast Cancer Cell Lines. Advances in Breast Cancer Research, 3, 100-105. doi: 10.4236/abcr.2014.33015.

[1]   Osuchowski, M., Johnson, V., He, Q. and Sharma, R. (2004) Alterations in Regional Brain Neurotransmitters by Silymarin, a Natural Antioxidant Flavonoid Mixture, in BALB/c Mice. Pharmaceutical Biology, 42, 384-389.

[2]   Kroll, D.J., Shaw, H.S. and Oberlies, N.H. (2007) Milk Thistle Nomenclature: Why It Matters in Cancer Research and Pharmacokinetic Studies. Integrative Cancer Therapies, 6, 110-119.

[3]   Davis-Searles, P.R., et al. (2005) Milk Thistle and Prostate Cancer: Differential Effects of Pure Flavonolignans from Silybum marianum on Antiproliferative end Points in Human Prostate Carcinoma Cells. Cancer Research, 65, 4448-4457.

[4]   Kiruthiga, P.V., Beema Shafreen, R., Karutha Pandian, S. and Pandima Devi, K. (2007) Silymarin Protection against Major Reactive Oxygen Species Released by Environmental Toxins: Exogenous H2O2 Exposure in Erythrocytes. Basic Clinical Pharmacology Toxicology, 100, 414-419.

[5]   Manna, S.K., Mukhopadhyay, A., Van, N.T. and Aggarwal, B.B. (1999) Silymarin Suppresses TNF-Induced Activation of NF-Kappa B, c-Jun N-terminal Kinase, and Apoptosis. Journal of Immunology, 163, 6800-6809.

[6]   Li, L.H., et al. (2007) Silymarin Enhanced Cytotoxic Effect of Anti-Fas Agonistic Antibody CH11 on A375-S2 Cells. Journal of Asian Natural Products Research, 9, 593-602.

[7]   Singh, R.P. and Agarwal, R. (2006) Prostate Cancer Chemoprevention by Silibinin: Bench to Bedside. Molecular Carcinogenesis, 45, 436-442.

[8]   Singh, R.P. and Agarwal, R. (2004) A Cancer Chemopreventive Agent Silibinin, Targets Mitogenic and Survival Signaling in Prostate Cancer. Mutation Research, 555, 21-32.

[9]   Zi, X., Grasso, A.W., Kung, H.J. and Agarwal, R. (1998) A Flavonoid Antioxidant, Silymarin, Inhibits Activation of erbB1 Signaling and Induces Cyclin-Dependent Kinase Inhibitors, G1 Arrest, and Anticarcinogenic Effects in Human Prostate Carcinoma DU145 Cells. Cancer Research, 58, 1920-1929.

[10]   Scambia, G., et al. (1996) Antiproliferative Effect of Silybin on Gynaecological Malignancies: Synergism with Cisplatin and Doxorubicin. European Journal of Cancer, 32A, 877-882.

[11]   Sharma, G., Singh, R.P., Chan, D.C. and Agarwal, R. (2003) Silibinin Induces Growth Inhibition and Apoptotic Cell Death in Human Lung Carcinoma Cells. Anticancer Research, 23, 2649-2655.

[12]   Zi, X., Feyes, D.K. and Agarwal, R. (1998) Anticarcinogenic Effect of a Flavonoid Antioxidant, Silymarin, in Human Breast Cancer Cells MDA-MB 468: Induction of G1 Arrest through an Increase in Cip1/p21 Concomitant with a Decrease in Kinase Activity of Cyclin-Dependent Kinases and Associated Cyclins. Clinical Cancer Research, 4, 1055-1064.

[13]   Deep, G., Oberlies, N.H., Kroll, D.J. and Agarwal, R. (2007) Isosilybin B and Isosilybin A Inhibit Growth, Induce G1 Arrest and Cause Apoptosis in Human Prostate Cancer LNCaP and 22Rv1 Cells. Carcinogenesis, 28, 1533-1542.

[14]   Roy, S., Kaur, M., Agarwal, C., Tecklenburg, M., Sclafani, R.A. and Agarwal, R. (2007) p21 and p27 Induction by Silibinin Is Essential for Its Cell Cycle Arrest Effect in Prostate Carcinoma Cells. Molecular Cancer Therapeutics, 6, 2696-2707.

[15]   Kaur, M., et al. (2009) Silibinin Suppresses Growth and Induces Apoptotic Death of Human Colorectal Carcinoma LoVo Cells in culture and Tumor Xenograft. Molecular Cancer Therapeutics, 8, 2366-2374.

[16]   Zhu, W., Zhang, J.S. and Young, C.Y. (2001) Silymarin Inhibits Function of the Androgen Receptor by Reducing Nuclear Localization of the Receptor in the Human Prostate Cancer Cell Line LNCaP. Carcinogenesis, 22, 1399-1403.

[17]   Jemal, A., et al. (2011) Global Cancer Statistics. CA: A Cancer Journal for Clinicians, 61, 69-90.

[18]   Ferlay, J., Soerjomataram, I., Ervik, M., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D.M., Forman, D. and Bray, F. (2013) GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer.

[19]   Mousavi, S.M., et al. (2007) Breast Cancer in Iran: An Epidemiological Review. The Breast Journal, 13, 383-391.

[20]   Noroozi, A., Jomand, T. and Tahmasebi, R. (2011) Determinants of Breast Self-Examination Performance among Iranian Women: An Application of the Health Belief Model. Journal of Cancer Education, 26, 365-374.

[21]   Bidgoli, S.A., Ahmadi, R. and Zavarhei, M.D. (2010) Role of Hormonal and Environmental Factors on Early Incidence of Breast Cancer in Iran. Science of the Total Environment, 408, 4056-4061.

[22]   Deep, G. and Agarwal, R. (2007) Chemopreventive Efficacy of Silymarin in Skin and Prostate Cancer. Integrative Cancer Therapies, 6, 130-145.

[23]   Gharagozloo, M. and Amirghofran, Z. (2007) Effects of Silymarin on the Spontaneous Proliferation and Cell Cycle of Human Peripheral Blood Leukemia T Cells. Journal of Cancer Research and Clinical Oncology, 133, 525-532.

[24]   Singh, R.P., et al. (2005) Silibinin Strongly Inhibits Growth and Survival of Human Endothelial Cells via Cell Cycle Arrest and Downregulation of Survivin, Akt and NF-kappaB: Implications for Angioprevention and Antiangiogenic Therapy. Oncogene, 24, 1188-1202.

[25]   Li, W., et al. (2011) Molecular Mechanism of Silymarin-Induced Apoptosis in a Highly Metastatic Lung Cancer Cell Line Anip973. Cancer Biotherapy and Radiopharmaceuticals, 26, 317-324.

[26]   Gu, M., Singh, R.P., Dhanalakshmi, S., Agarwal, C. and Agarwal, R. (2007) Silibinin Inhibits Inflammatory and Angiogenic Attributes in Photocarcinogenesis in SKH-1 Hairless Mice. Cancer Research, 67, 3483-3491.

[27]   Rajamanickam, S., Velmurugan, B., Kaur, M., Singh, R.P. and Agarwal, R. (2010) Chemoprevention of Intestinal Tumorigenesis in APCmin/+ Mice by Silibinin. Cancer Research, 70, 2368-2378.

[28]   Kim, S., et al. (2011) Silibinin Suppresses EGFR Ligand-Induced CD44 Expression through Inhibition of EGFR Activity in Breast Cancer Cells. Anticancer Research, 31, 3767-3773.

[29]   Provinciali, M., et al. (2007) Effect of the Silybin-Phosphatidylcholine Complex (IdB 1016) on the Development of Mammary Tumors in HER-2/Neu Transgenic Mice. Cancer Research, 67, 2022-2029.