Evaluation of chemo-sensitizing effects of silibinin in paclitaxel-resistant breast cancer cells

Abstract

Introduction: Drug resistance is one of the main causes of treatment failure and mortality in cancer patients. Silibinin, a non-toxic natural substance with a long history of medical uses, is a flavanone from Silybum marianum seeds. 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. Recent studies show that silibinin can enhance cytotoxic effects of chemotherapeutic agents in a variety of human cancers. Paclitaxel 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. Aim: The aim of this project was to evaluate the chemo-sensitizing effects of silibinin in wild type & paclitaxel-resistant MCF-7 cells. Methods: Growth inhibitory and anti-proliferative effects of silibinin were assessed by MTT assay. Annexin V/PI staining was used to evaluate the induction of apoptosis by silibinin. Results: Silibinin potently inhibited the growth of wild type & paclitaxel-resistant MCF-7 cells with IC50 being 217.6µM and 572.3nM, respectively. Interestingly, silibinin enhances the cytotoxic effects of paclitaxel in both wild type and paclitaxel-resistant MCF-7 cells and induces a synergistic growth inhibitory effect in the cells treated with paclitaxel in combination with silibinin. We also found that treatment of paclitaxel-resistant MCF-7 cells with silibinin alone or in combination with paclitaxel resulted in a significant increase in the percentage of early and late apoptotic cells indicating an induction apoptosis by silibinin in these drug resistant cells. Conclusion: In conclusion our findings show that silibinin can be a useful drug for treatment of drug resistant breast cancers.