Arsenal of Phytochemicals to Combat Against Arsenic-Induced Mitochondrial Stress and Cancer.

Significance: Phytochemicals are important dietary constituents with antioxidant properties. They affect various signaling pathways involved in the overall maintenance of interior milieu of the cell. Arsenic, an environmental toxicant, is well known for its deleterious consequences, such as various diseases, including cancers in humans. Mitochondria are the cell's powerhouse that fuel all metabolic energy requirements. Dysfunctional mitochondria due to stressors may lead to abnormal functioning of the organelle, hampering the crucial cellular cross talks and ultimately leading to cancer. Application of phytochemicals against arsenic-induced mitochondrial disorders may be a preventive measure to counteract the ruinous impacts of the metalloid. Recent Advances: In recent years, extensive research on the role of mitochondria in cancer gives a better understanding of the areas the organelle covers in maintaining a healthy cell or in inducing carcinogenicity. Detailed knowledge of the mitochondrial governances would enable researchers to administer numerous phytochemicals to ameliorate altered oxidative phosphorylation, mitochondrial membrane potential (MMP), mitochondrial oxidative stress, unfolded protein response, glycolysis, or even apoptosis. Critical Issues: In this review, we have addressed how various phytochemicals belonging to diverse classes combat against arsenic-induced mitochondrial oxidative stress, depletion of MMP, cell cycle abrogation, apoptosis, glycolytic damages, oncogenic regulations, chaperones, mitochondrial complexes, and mitochondrial membrane pore formation in both in vitro and in vivo models. Future Directions: Insightful application of mitoprotective phytochemicals against arsenic-induced mitochondrial oxidative stress and carcinogenesis may guide researchers to develop preclinical chemopreventive agents to fight arsenic toxicity in humans.