Panchuk R. Molecular mechanisms of the influence of antioxidants on the action of anticancer drugs towards malignant cells

Object of study: Induction of apoptosis and oxidative stress by antitumor drugs in malignant cells in vitro and in laboratory animals with experimental tumors. The aim of the work: to find out the mechanisms of cytoprotective activity of a number of antioxidants under the action of well-known anticancer drugs, to increase their effectiveness by immobilizing these drugs on nano-sized carriers, and study of the possibility of using experimental antitumor drugs in combination with some antioxidants to suppress the growth of multidrug drug-resistant tumor cells. Methods: cellular-biological, biochemical, bioinformatical. For the first time it has been proposed to co-immobilize antitumor drug and antioxidant on a nanosized carrier to achieve a synergistic effect, which led to a 4-fold increase in the therapeutic effect of this nanocomplex and a 2-fold reduction in the manifestations of its negative side effects on the body of tumor-bearing animals. It has been demonstrated that the unique ability of angucycline antibiotics of the landomycin family to overcome the acquired resistance of tumors to drugs is due to their thiol-targeting activity, as well as binding to NADPH-dehydrogenase NQO1. This leads to early (1 hour) production of hydrogen peroxide, activation of effector caspase-7, and subsequent induction of apoptosis without involvement of mitochondria.