1. Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
Abstract
Introduction
Breast cancer is the principle cause of cancer mortality in females. mitomycin c (mmc), as a potent antitumor drug, is used for the treatment of different cancer cells, however adverse effects and resistance of cancer cells have limited the application of mmc, and combination of mmc with novel biological agents are commonly proposed. recent studies indicate that lithium, an fda-approved mood stabilizer drug, possesses antitumor effects in different malignancies, however, whether lithium could enhance mmc-induced apoptosis in breast cancer has not been examined.
Methods
In this study, the effect of mmc alone and combined with licl on mda-mb-231 breast cancer cells viability was measured by mtt assay. apoptosis was detected with flow cytometry and western blot analysis of parp cleavage.
Results
Mtt assay demonstrated reduction of cells viability upon exposure to mmc with an ic50 value of 20 µm. various concentrations of licl alone had no cytotoxic effect on the cells whereas combined treatment with licl and mmc, induced synergistic cytotoxicity with ic50 value of 5 µm. licl increased mmc-induced parp cleavage to its 89 and 24 kda fragments. following treatment with mmc, the percentage of apoptotic and necrotic cells was increased compared to the control as detected by flow cytometry. whereas when the cells pretreated with licl, apoptosis increased significantly while necrosis was negligible.
Conclusion
In conclusion, present study demonstrates that licl enhances mmc-induced apoptosis in mda-mb-231 cells and provides new insights into the mechanism of licl action in cell death.
Keywords
Lithium chloride, mitomycin c, breast cancer cells, apoptosis
