RBI Scientists Anamaria Brozović, PhD, Andreja Ambriović-Ristov, PhD, and Maja Osmak, PhD, from the Laboratory for Genotoxic Agents, Department of Molecular Biology have published a review article entitled The relationship between cisplatin-induced reactive oxygen species, glutathione, and BCL-2 and resistance to cisplatin (IF 7,204) in the journal Critical Reviews in Toxicology, which is one of the most respected journals in the field of toxicology.

This review article describes the role and relationship of the anti-apoptotic protein BCL-2 and glutathione in cisplatin-induced oxidative stress as well as the role these molecules play in cisplatin resistant tumor cells. Despite the generally accepted fact that DNA damage is key for the harmful effects of cytostatics, this review article presents the results of recent studies that show that cisplatin can induce production of lethal reactive oxidative radicals (ROS) that are not primarily related to DNA damage.

The idea for this review article arose from our results published in Molecular Pharmacology in 2008. In that article entitled alpha(v)beta(3) Integrin-mediated drug resistance in human laryngeal carcinoma cells is caused by glutathione-dependent elimination of drug-induced reactive oxidative species it was shown that in laryngeal cancer cells, cisplatin induces the continuous production of ROS, and increases the concentrations of anti-oxidant molecules, such as glutathione which inactivates ROS and thus protects cells from death.