Oxidative Stress, Antioxidant Status, and Redox Signaling in Carcinogenesis

An increase in ROS production or a decrease in ROS-scavenging capacity due to exogenous stimuli or endogenous metabolic alterations can disrupt redox homeostasis, leading to an overall increase of intracellular ROS levels or oxidative stress. Oxidative stress promotes damage to the cell structure including proteins, lipids, membranes, and DNA, strongly implicating such damage in the etiology of cancer. The extent to which oxidative damage contributes to the process of carcinogenesis is not yet clear. Besides the role of oxidants in the induction of mutations, it is apparent that ROS mediate cell-signaling pathways that are involved in cell growth regulatory pathways and are thus instrumental in the process of carcinogenesis. The activation of transcription factors including MAP-kinase/AP-1 and NF-κB pathways has a direct effect on cell proliferation and apoptosis. Thus damage, mutations, and altered gene expression are all key players in the process of carcinogenesis. The involvement of oxidants appears to be the common denominator to all these events supporting the idea that tumor microenvironment plays an important role in cancer initiation and progression. An altered pro-oxidant–antioxidant balance may lead to an increased oxidative damage and consequently play an important role in the carcinogenesis. Significantly raised NF-κB activation, VEGF level, and cell proliferation index in carcinoma indicate definite correlation of oxidative stress and carcinogenesis. Biomarkers of oxidative stress have the potential to help establish pathogenic stage and risk for disease.