Pitavastatin Enhances Doxorubicin-induced Apoptosis in MCF7 Breast Cancer Cells

Abstract

Breast cancer is the most common malignancy in women worldwide. While doxorubicin is part of the standard therapy for metastatic breast cancer, it has limited success. Pitavastatin has been shown to enhance the anti-cancer activity of certain therapeutics. The current study, therefore, explored the anti-cancer activity of the combined treatment of doxorubicin and pitavastatin in MCF7 breast cancer cells. Cell proliferation and viability assays demonstrated that combined doxorubicin and pitavastatin treatment resulted in synergistic cytotoxicity and cell death. Western blotting analysis showed that pitavastatin treatment resulted in increasing levels of p53 and the cell cycle regulator p21 in both doxorubicin treated and untreated cells. Furthermore, we demonstrated that apoptosis induced by the combined treatment occurs through the intrinsic pathway as evident from the activation of caspase 9, caspase 7 and the reduction of BCL-2 level. This study provides novel evidence to suggest that combined treatment of doxorubicin and pitavastatin may be effectively combined to treat breast cancer with the potential to minimize the side effects associated with high doses of doxorubicin.Breast cancer is the most common malignancy in women worldwide. While doxorubicin is part of the standard therapy for metastatic breast cancer, it has limited success. Pitavastatin has been shown to enhance the anti-cancer activity of certain therapeutics. The current study, therefore, explored the anti-cancer activity of the combined treatment of doxorubicin and pitavastatin in MCF7 breast cancer cells. Cell proliferation and viability assays demonstrated that combined doxorubicin and pitavastatin treatment resulted in synergistic cytotoxicity and cell death. Western blotting analysis showed that pitavastatin treatment resulted in increasing levels of p53 and the cell cycle regulator p21 in both doxorubicin treated and untreated cells. Furthermore, we demonstrated that apoptosis induced by the combined treatment occurs through the intrinsic pathway as evident from the activation of caspase 9, caspase 7 and the reduction of BCL-2 level. This study provides novel evidence to suggest that combined treatment of doxorubicin and pitavastatin may be effectively combined to treat breast cancer with the potential to minimize the side effects associated with high doses of doxorubicin