Melatonin suppresses tumor angiogenesis by inhibiting HIF-1α stabilization under hypoxia

In this study, we found that melatonin, a small lipophilic molecule secreted primarily by the pineal gland, destabilizes hypoxia-induced HIF-1[alpha] protein levels in the HCT116 human colon cancer cell line. This destabilization of HIF-1[alpha] resulted from the antioxidant activity of melatonin against ROS induced by hypoxia. Moreover, under hypoxia, melatonin suppressed HIF-1 transcriptional activity, leading to a decrease in VEGF expression. Melatonin also blocked in vitro tube formation and invasion and migration of human umbilical vein endothelial cells induced by hypoxia-stimulated conditioned media of HCT116 cells. These findings suggest that melatonin could play a pivotal role in tumor suppression via inhibition of HIF-1-mediated angiogenesis. (Source: Journal of Pineal Research)

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