Effects of topotecan on antioxidant enzymes in MCF -7 cell line

ABSTRACT Breast cancer is the second most common cancer among women in developed countries. Topotecan, a new camptothecin analogue [9-(dimethyl amino) methyl-10-hydroxy camptothecin], is giving hope in the treatment of breast cancer. The cytotoxic activity of topotecan in human tumor cells depends on the stabilization of topoisomerase 1 and DNA complex. Reactive oxygen species (ROS) are cytotoxic products of normal cellular metabolism. Many antineoplastic agents eliminate tumor cells by inducing programmed cell death or apoptosis, and numerous investigations have documented the cellular changes resulting from oxidative stress induced in cells following exposure to cytotoxic drugs. Although some of cytotoxic agents have different structures and targets, they increase the levels of ROS. However, it has not been studied yet that topotecan causes oxidative stress in tumor cells. The aim of this study was to investigate the effect of topotecan on antioxidant enzymes and oxidative stress in the human breast cancer cell line (MCF-7). Determining the oxidant effect of topotecan can elucidate possible alternative mechanism of drug cytotoxicity. Therefore, MCF-7 cells were treated with topotecan for 24 hours and levels of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px)], lipid peroxidation [MDA], oxidative protein damage [carbonyl content], reduced glutathione [GSH] and sulphdryl were determined. The obtained data indicate a state of oxidation, as revealed by increased lipid peroxidation and protein oxidation ratios, in MCF-7 cells exposed to topotecan compared to the non-treated control group. Levels of non- enzymatic antioxidants (GSH, sulphdryl content) decreased significantly in MCF-7 cells treated with topotecan compared to controls. Compared to the control cell line, there was a slight increase in SOD and a significant increase in GSH-Px and catalase activity in MCF-7 cells treated with topotecan. These result support the probability of ROS formation in cells exposed to topotecan and suggest an alternative mechanism for topotecan cytotoxicity.