Level of Oxidative Stress: A Fate-Determiner of Carcinogenesis and Anti-Carcinogenesis

Molecular oxygen, a double-edged sword, is both a boon and a curse for the existence of life. Oxidative stress is the disequilibrium between reactive oxygen (ROS)-generation and elimination that inflicts cellular damage. Living cells can adapt to the ever-changing internal or external stresses. However, they gradually lose their radical-scavenging adaptability with persistent stress, which further increases during neoplasia. Cancer cells, well adapted in pro-oxidative milieu, drive metabolic and genomic reprogramming, which further escalates the oxidative load. This vicious cycle promotes further carcinogenic alterations. Contrastingly, the same ROS is essential for the oxidative-burst mediated anticancer host-defense. To sustain this redox pressure, cancer cells hijack the intracellular antioxidants. Therefore, redox reorientation towards enhanced responsiveness may selectively target malignant cells by ROS-enhancement beyond tolerance leading to mortality. Carcinogenesis, a multistep process, requires ROS during initiation, promotion and progression. However, supraphysiological ROS may induce apoptosis in unmanageable malignancies. Interestingly cells possess an evolutionary-conserved nature to get hormetically pre-conditioned by a transient ultralow exposure of a stressor, which in higher dose may show the opposite effect. Antioxidants are excellent chemopreventives and chemotherapeutics. Here, we have condensed the possible anticancer modulation of oxidative stress by phytochemicals, aiming at an insight for future strategies in cancer management.

Keywords: Anticancer Therapy, Antioxidant, Carcinogenesis, Dietary Phytochemicals, Hormesis, Nuclear Factor (Erythroid-Derived 2)-Like 2 (Nrf2), Oxidative Stressor, Prooxidant, Reactive Oxygen Species, Xenobiotic Metabolism.