The Effect of Rapamycin on Oxidative Stress in MCF-7 and MDA MB-231 Human Breast Cancer Cell Lines

Abstract

Background: Mammalian target of rapamycin (mTOR) is a kinase pathway that regulates the cell cycle progression and growth. Rapamycin inhibits this pathway. The useful effects of rapamycin on cell growth have been widely shown in animal studies. However, its beneficial effects are associated with some success in benign and malignant cancers, which have produced its moderate outcomes in the clinic. Objectives: The aim of this study was to investigate whether rapamycin can induce oxidative stress in MCF-7 and MDA MB-231 human breast cancer cell lines. Methods: The MCF-7 and MDA MB-231 cell lines were cultivated and treated with rapamycin for 72 hours. The viability of the cells was determined using the colorimetric MTT assay. Lipid peroxidation (TBARS), protein oxidation (carbonyl groups), total antioxidant capacity assay, and glutathione (GSH) levels were measured in the MCF-7 and MDA MB-231 cells both with and without rapamycin treatment. Results: The IC50 concentration of rapamycin was 100 nM in MCF-7 cells, whereas the MDA-MB-231 cells were highly resistant to rapamycin. Our data indicated an increase in oxidative status by increasing lipid peroxidation and protein oxidation, GSH, and total antioxidant capacity levels in the MCF-7 and MDA-MB-231 cell lines exposed to rapamycin in comparison with control cells. Conclusions: These outcomes support our theory that rapamycin increases oxidative stress in MCF-7 and MDA MB-231 cells but also shows high levels of antioxidant effects, which probably limit the effects of the rapamycin on the same issue in the clinic.