Induction of Oxidative Stress in Tumor Cells: A New Strategy for Drug Therapy of Malignant Tumors

Abstract

Abstract—Tumor cells have a higher basal ROS level than normal cells. This phenomenon may provide grounds for the development of novel antitumor drugs that are capable of selectively inducing oxidative stress in tumor cells. This approach can involve agents that induce ROS production and/or inhibit cellular enzymatic antioxidant systems. Thioredoxin reductase is a key enzyme in such systems. Overexpression of thioredoxin reductase has been shown in several types of tumors of hematopoietic, lymphoid, and other tissues. The results of studies of the antitumor activities of various synthetic and natural substances that are able to inhibit thioredoxin reductase are summarized. It is shown that thioredoxin reductase inhibition results in an increase in ROS level in tumor cells and oxidative damage of cells followed by apoptosis mainly via the mitochondrial pathway.