- Volume 17 Issue 5
DOI QR Code
Comparative Evaluation of Silibinin Effects on Cell Cycling and Apoptosis in Human Breast Cancer MCF-7 and T47D Cell Lines
- Jahanafrooz, Zohreh (Department of Cellular and Molecular Biology, School of Biology, University of Tehran) ;
- Motameh, Nasrin (Department of Cellular and Molecular Biology, School of Biology, University of Tehran) ;
- Bakhshandeh, Behnaz (Department of Biotechnology, College of Science, University of Tehran)
- Published : 2016.05.01
Silibinin is a natural polyphenol with high antioxidant and anticancer properties. In this study, its influence on two of the most commonly employed human breast cancer cell lines, MCF-7 and T47D, and one non-malignant MCF-10A cell line, were investigated and compared. Cell viability, the cell cycle distribution and apoptosis induction were analyzed by MTT and flow cytometry, respectively. The effect of silibinin on PTEN, Bcl-2, P21, and P27 mRNAs expression was also investigated by real-time RT-PCR. It was found that silibinin caused G1 cell cycle arrest in MCF-7 and MCF-10A cells but had no effect on the T47D cell cycle. Silibinin induced cytotoxic and apoptotic effects in T47D cells more than the MCF-7 cells and had no cytotoxic effect in MCF-10A cells under the same conditions. Silibinin upregulated PTEN in MCF-7 and caused slightly increased P21 mRNA expression in T47D cells and slightly increased PTEN and P21 expression in MCF-10A cells. Bcl-2 expression decreased in all of the examined cells under silibinin treatment. P27 mRNA expression upregulated in T47D and MCF-10A cells under silibinin treatment. PTEN mRNA in T47D and P21 and P27 mRNAsin MCF-7 were not affected by silibinin. These results suggest that silibinin has mostly different inhibitory effects in breast cancer cells and might be an effective anticancer agent for some cells linked to influence on cell cycle progression.
Breast cancer cells;silibinin;bcl-2;cell cycling;PTEN;P21;P27
Supported by : University of Tehran
- Adams LM, Warburton MJ, Hayman AR (2006). Human breast cancer cell lines and tissues express tartrate-resistant acid phosphatase (TRAP). Cell Biol Int, 31,191-5.
- Agarwal C, Singh RP, Dhanalakshmi S, et al (2003). Silibinin upregulates the expression of cyclin-dependent kinase inhibitors and causes cell cycle arrest and apoptosis in human colon carcinoma HT-29 cells. Oncogene, 22, 8271-82. https://doi.org/10.1038/sj.onc.1207158
- Ahmad A (2013). Pathways to Breast Cancer Recurrence. ISRN Oncol, 2013, 1-16.
- Asad SF, Singh S, Ahmad A, Hadi SM (1998). Flavonoids: Antioxidants in diet and potential anticancer agents. Med Sci Res, 26, 723-28.
- Deep G, Agarwal R (2007). Chemopreventive efficacy of silymarin in skin and prostate cancer. Integr Cancer Ther 6, 130-45. https://doi.org/10.1177/1534735407301441
- Duan WJ, Li QS., Xia MY, et al (2011). Silibinin activated p53 and induced autophagic death in human fibrosarcoma HT1080 cells via reactive oxygen species-p38 and c-Jun N-terminal kinase pathways. Biol Pharm Bull, 34, 47-53. https://doi.org/10.1248/bpb.34.47
- Kaina B (2003). DNA damage-triggered apoptosis: critical role of DNA repair, double-strand breaks, cell proliferation and signaling. Biochem Pharmacol, 66, 1547-54. https://doi.org/10.1016/S0006-2952(03)00510-0
- Li L, GaoY , Zhang L, et al (2008). Silibinin inhibits cell growth and induces apoptosis by caspase activation, down-regulating survivin and blocking EGFR-ERK activation in renal cell carcinoma. Cancer Lett, 272, 61-9. https://doi.org/10.1016/j.canlet.2008.06.033
- Li LQ, Li XL, Wang L, et al (2012). Matrine inhibits breast cancer growth via miR-21/PTEN/Akt pathway in MCF-7 cells. Cell Physiol Biochem, 30, 631-41. https://doi.org/10.1159/000341444
- Lu Y, Lin YZ, LaPushin R, et al (1999). The PTEN/MMAC1/TEP tumor suppressor gene decreases cell growth and induces apoptosis and anoikis in breast cancer cells. Oncogene, 18, 7034-45. https://doi.org/10.1038/sj.onc.1203183
- Mokhtari MJ, Motamed N, Shokrgozar M (2008). Evaluation of silibinin on the viability, migration and adhesion of the human prostate adenocarcinoma (PC-3) cell line. Cell Biol Int, 32, 888-92. https://doi.org/10.1016/j.cellbi.2008.03.019
- Roy S, Kaur M, Agarwal C, et al (2007). p21 and p27 induction by silibinin is essential for its cell cycle arrest effect in prostate carcinoma cells. Mol Cancer Ther, 6, 2696-707. https://doi.org/10.1158/1535-7163.MCT-07-0104
- Sharma G, Singh RP, Chan DC, Agarwal R (2003). Silibinin induces growth inhibition and apoptotic cell death in human lung carcinoma cells. Anticancer Res, 23, 2649-55.
- Tiwari P, Kumar A, Balakrishnan S, Kushwaha HS, Mishra KP (2011). Silibinin-induced apoptosis in MCF7 and T47D human breast carcinoma cells involves caspase-8 activation and mitochondrial pathway. Cancer Invest, 29, 12-20. https://doi.org/10.3109/07357907.2010.535053
- Vojtesek B, Lane DP (1993). Regulation of p53 protein expression in human breast cancer cell lines. J Cell Sci, 105, 607-12.
- Wang HJ, Wei XF, Jiang YY, et al (2010). Silibinin induces the generation of nitric oxide in human breast cancer MCF-7 cells. Free Radic Res, 44, 577-84. https://doi.org/10.3109/10715761003692495
- Weng LP, Brown JL, Eng C (2001). PTEN coordinates G(1) arrest by down-regulating cyclin D1 via its protein phosphatase activity and up-regulating p27 via its lipid phosphatase activity in a breast cancer model. Hum Mol Genet, 15, 599-604.
- Zi X, Agarwal R (1999). Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: Implications for prostate cancer intervention. Proc Natl Acad Sci USA, 96, 7490-95. https://doi.org/10.1073/pnas.96.13.7490
- Zi X, Feyes DK, 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. Clin Cancer Res, 4, 1055-64.