Roles of NAD (P) H-Quinone Oxidoreductase 1 (NQO1) On Cancer Progression and Chemoresistance

Abstract

NAD(P)H-Quinone Oxidoreductase 1 (NQO1), originally referred to as DT-diaphorase, is a xenobiotic metabolizing/antioxidant enzyme that detoxifies chemical stressors, providing cytoprotection in normal tissues. NQO1 catalyzes obligatory two-electron reduction of several endogenous and environmental quinones to hydroquinone that are ready for further conjugation and excretion. The enzyme requires NADH or NADPH as an electron donor for enzymatic activity. High-level of NQO1 expression has however, been correlated with numerous human malignancies, suggesting its role in cancer progression and chemoresistance. This adaptation renders the cancer cells to survive in relatively high oxidative stress condition compared to normal cells, as well as protects cancer cells from toxic action of chemotherapeutic agents. Inhibitors of NQO1 enzyme have been found to improve anticancer activities of conventional chemotherapeutic agents. The review provides a perspective on a molecular basis of NQO1-mediated cancer cells progression and the suppression and possible strategy to improve chemosensitivity and to overcome chemoresistance of NQO1 inhibitors when used in combination with chemotherapeutic drugs.