Melatonin: An atypical hormone with major functions in the regulation of angiogenesis

Melatonin (N-acetyl-5-methoxytryptamine), a pleotropic molecule with a wide distribution, has received considerable attention in recent years, mostly because of its various major effects on tissues or cells since it has both receptor-dependent and receptor-independent actions over a wide range of concentrations. These biological and physiological functions of melatonin include regulation of circadian rhythms by modulating the expression of core oscillator genes, scavenging the reactive oxygen species and reactive nitrogen species, modulating the immune system and inflammatory response, and exerting cytoprotective and antiapoptotic effects. Given the multiple critical roles of melatonin, dysregulation of its production or any disruption in signaling through its receptors may have contributed in the development of a wide range of disorders including type 2 diabetes, aging, immune-mediated diseases, hypertension, and cancer. Herein, we focus on the modulatory effects of melatonin on angiogenesis and its implications as a therapeutic strategy in cancer and related diseases.