MCF-7 and its Multidrug Resistant Variant MCF-7/ADR Overcome TNF Cytotoxicity through Prevention of Reactive Oxygen Species Accumulation

Background: Signal transduction of numerous cytokines and growth factors are mediated by reactive oxygen species (ROS). Tumor necrosis factor-alpha (TNF-alpha) have stimulated accumulation of ROS in various in vitro studies. MCF-7 and its Adriamycin resistant variant MCF-7/ADR are resistant against TNF-alpha cytotoxicity. Role of ROS in the resistance of MCF-7 and MCF-7/ADR cells was investigated. Methods: ROS accumulation and viability in MCF-7 and MCF-7/ADR after TNF-alpha exposure was evaluated using 2',7'-dichlorofluorescein diacetate (DCFH-DA) as a fluorescent probe and 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide (MTT) cytotoxicity assay respectively. Results: ROS level did not change significantly after TNF-alpha exposure. Induction of ROS accumulation along with TNF-alpha treatment sensitized these cells to TNF-alpha toxicity. Conclusion: It can be concluded that lack of ROS accumulation following TNF-alpha exposure is involved at least by part in the resistance of MCF-7 and its drug resistant derivative MCF-7/ADR cells to TNF-alpha cytotoxicity.