Melatonin Prevents Tumor Growth: The Role of Genes Controlling the Circadian Clock, the Cell Cycle, and Angiogenesis

Abstract

Recent evidence highlights the protective role of melatonin in a variety of pathological conditions, including multiple types of cancer. Epidemiological studies increasingly suggest that exposure to light at night suppresses melatonin synthesis in night-shift and rotating-shift workers, potentially elevating their risk of cancer development. Experimental data further indicate that melatonin can inhibit the proliferation of tumor cells, including glioblastoma-like stem cells. In the present study, we investigated the effect of melatonin on the expression of genes involved in regulating the circadian rhythm, cell cycle progression, and angiogenesis in rats exposed to constant light, a model of circadian disruption. Our findings demonstrate that melatonin administration significantly inhibited tumor growth and reduced the vascularization associated with circadian rhythm disturbance. Molecular analysis revealed that melatonin altered the circadian expression of several genes affecting tumor biology, including p53, TNF-α, Per2, VEGF-A, PDGF-C, and Ang, which are involved in circadian rhythms, cell cycle, and angiogenesis regulation. These results strengthen the existing hypothesis that circadian disruption contributes to tumor progression and suggest that melatonin exerts anticancer effects by modulating circadian gene expression and angiogenesis. Our findings provide further insight into the mechanism by which melatonin may exert oncostatic effects and highlight its potential as a therapeutic agent in cancers associated with circadian rhythm disruption.