Synergistic anti-cancer effects of silibinin-etoposide combination against human breast carcinoma MCF-۷ and MDA-MB-۲۳۱ cell lines

Objective(s): Recently, there is a significant focus on combination chemotherapy for cancer using a cytotoxic drug and a phytochemical compound. We investigated the effect of silibinin on etoposide-induced apoptosis in MCF-۷ and MDA-MB-۲۳۱ breast carcinoma cell lines.Materials and Methods: The cytotoxic effects of silibinin and etoposide were determined using MTT assay after ۲۴ and ۴۸ hr incubation with these drugs individually and combined. The mRNA expression of Bax and Bcl۲, and protein levels of P۵۳, phosphorylated p۵۳ (P-P۵۳), and P۲۱ were determined using real-time PCR and western blot analysis, respectively. The caspase ۹ activity was measured using an ELISA kit. Results: Silibinin and etoposide alone and combined significantly inhibit cell growth in a dose and time-dependent manner in both cell lines. The strongest synergistic effects in terms of MCF-۷ cell growth inhibition [combination index (CI) = ۰.۰۶۶] were evident. The silibinin-etoposide combinations cause a much powerful apoptotic death (۴۷% and ۴۰%) compared with each compound individually in MCF-۷ and MDA-MB ۲۳۱ cells, respectively. Additionally, the silibinin-etoposide combinations significantly increased the expression of P۵۳, P-P۵۳, and P۲۱ in MCF-۷ cells. Neither silibinin nor etoposide individually increased the level of P۵۳ and P-P۵۳ in MDA-MB-۲۳۱ cells, but both of them individually and combined increased the level of P۲۱.Conclusion: Since the silibinin-etoposide combination induces apoptosis in both cell lines with and without expression of p۵۳, thus, it is suggested that this combination may be a successful therapeutic strategy for breast cancer regardless of P۵۳ status.

Keywords:

Apoptosis , Breast Cancer , Drug synergism , Etoposide , MCF-۷ cells , Silibinin