The dual-actions of melatonin as a potential oncostatic agent and a protector against chemotherapy-induced toxicity

Cancer is one of the most complicated and arduous diseases, causing immense physical and emotional tribulations in the life of patients. Carcinogens can lead to genetic mutations and cancer progression either by directly binding to DNA covalently, forming cross-links, or indirectly via the generation of oxidative stress and/or by other recondite mechanisms. Despite being the most widely used treatment, chemotherapy has several adverse consequences, including acute and/or chronic toxicities. Numerous studies have demonstrated melatonin being a potential anticancer molecule with multiple activities including prevention of the initiation, promotion, and progression of cancer. In addition to its role as a potent antioxidant, melatonin exhibits its cytostatic effects by arresting the mutated cell in the G0/G1 phase, preventing epithelial-to-mesenchymal transition and inciting the immune battle against tumours, possibly by dampening MMP activities. Melatonin inhibits the MAP-K/ERK and p38 pathways and regulates NF-ĸB-mediated inflammatory responses. Melatonin exerts its anti-angiogenic activity by curbing VEGF levels, while its anti-estrogenic activity by inhibiting the cellular uptake of linoleic acid (LA). In addition, melatonin reduces the toxicities of the chemotherapy while improving its effectiveness in cancer treatment. The purpose of this review is to assemble the knowledge available on melatonin’s oncostatic role and its protective effects against chemotherapy-induced toxicities. Further studies are needed to investigate the adjunctive role of melatonin with chemotherapy in the clinical setting and to corroborate its effectiveness in cancer cure.