P-48 - Redox-active quinones as regulators of free radical processes and potential antitumor agents

Abstract

Redox regulation of cell activity is the basis for antitumor therapy. In cancer cells generation of ROS is reduced, thus such cells have resistance to apoptotic signals. Malignant cells reproduce under hypoxic conditions and this fact reduces the probability of oxidative processes. Therefore, the use of oxidizing agents, such as quinones and their derivatives, is significant, because of their capability to provide additional formation of ROS, cytotoxic oxidation products and oxidative destruction of biomolecules. We have shown that p-benzoquinone and its derivatives are effective regulators of free radical processes involving hydroxyl-containing C-centered radicals. Thymoquinone, a biologically active component of Nigella sativa, and other p-benzoquinones inhibit ROS-induced fragmentation of glycerophospholipids, significantly suppressing the formation of phosphatidic acid, which in cancer cells should reduce the effectiveness of antitumor therapy. It was found that p-benzoquinones inhibit the growth of HEp-2 cells in a dose-dependent manner. The tested quinones possess antitumor activity due to their ability to suppress the mitochondrial membrane potential. Possible relationship between radical-regulatory and antitumor properties of quinoid-type compounds is proposed.