Synergistic antitumor effects of lithium and mitomycin C on MDA-MB-231 breast cancer cells

Introduction & Aim: Breast cancer is the leading cause of cancer death in females. Mitomycin C (MMC), an anticancer drug, is used to treat breast cancers, however the clinical use of MMC has limited due to appearance of side effects and resistance of cancer cells, and combination of MMC with other biological agents is commonly proposed. Recent studies indicate that lithium, an FDA-approved mood stabilizer drug, possesses antitumor effects in different malignancies. The aim of this study is to investigate whether lithium chloride (LiCl) potentiates the cytotoxicity of MMC on human breast cancer cells. Methods: MDA-MB-231 cells were cultured in RPMI supplemented 10% FBS and incubated in 5% CO2 at 37°C. Then we determined the cytotoxicity effect of MMC alone and combined with lithium chloride (LiCl) using MTT assay after 24 h incubation. To test if MMC plus LiCl inhibit the tumorigenic potential of the cells, we performed colony-forming assay. Analysis of apoptotic cell death carried out by anion superoxide production and flow cytometry.Results: The results showed that LiCl significantly increased MMC-induced Cell death. The reduced colony number by MMC was more evident when the cells were pre-incubated with LiCl. LiCl increased MMC-induced anion superoxide production, prevented MMC-induced necrosis and switches the cell death mode to apoptosis as detected by flow cytometry. Conclusion: In conclusion, LiCl efficiently enhances cytotoxicity, apoptotic cell death and safety of MMC, and this combination has the potential to develop a new anticancer regimen for the treatment of breast cancer.

Keywords:

breast cancer cells , Lithium , Mitomycin C , cytotoxicity , Apoptosis