Studying the effects of silibinin on the expression of proteins involved in cell apoptosis in paclitaxel-resistant MCF-7 breast cancer cells

Abstract

Introduction: Drug resistance is one of the main causes of treatment failure and mortality in cancer patients. Silibinin, a flavanone from Silybummarianumseeds , has long history of medical uses due to its hepatoprotective effects.Silibinin has potent antioxidant effect and its anticancer activity has been shown in several in vivo and in vitro models. Silibinin is currently under phase II clinical trial in prostate cancer patients. One of the main advantages of silibinin is its safety and low toxicity in humans. While several studieshave shown that silibinin can enhance cytotoxic effects of chemotherapeutic agents in a variety of human cancers, only few studies have evaluated its anticancer effects on cancer cells resistant to chemotherapeutic agents. Paclitaxel (PAC) is one of the most widely used chemotherapeutic drugs in treatment of human malignancies including breast cancer but its clinical efficacy has been hampered due to development of drug resistance. One of the important mechanism by which cancer cells become resistant to PAC is dysregulation of proteins involved in apoptosis. Aim: The aim of this project was to evaluate the effects of silibinin on the expression of genes involved in cell apoptosis in paclitaxel-resistant MCF-7 breast cancer (MCF-7/PAC) cells. Methods: Expression levels of genes involved in cell apoptosis were assessed by real time–RT PCR method. Results:Silibinin potently reduced the expression level of anti-apoptotic genes(i.e Bcl2 and survivin) and increased the expression level of Bax which is a pro-apoptotic gene. These findings correlate with our previous unpublished data showing that silibinin significantly enhances the cytotoxic effects of PACin MCF-7/PAC cells. Conclusion: In conclusion, our findings show that silibinin can be a useful drug for treatment of breast cancers especially those resistant to PAC.