Angiogenesis is the process of new blood vessel formation, regulated by a number of pro- and antiangiogenic
factors and usually begins in response to hypoxia. Exogenous administration of melatonin has shown
numerous anti-tumor effects and appears to inhibit tumor angiogenesis. However, many factors involved in the
anti-angiogenic effect of melatonin are still under investigation. Here, we evaluate the effects of melatonin on cell
viability and expression of angiogenic factors in MCF-7 and MDA-MB-231 breast cancer cells under hypoxic conditions. Cell viability
was investigated by MTT and gene and protein expression of the hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth
factor (VEGF-A) were verified by qPCR and immunocytochemistry after melatonin treatment (1 mM) under hypoxic conditions.
Additionally, a protein array with 20 different cytokines/factors was performed on tumor cell lysates. The results showed that 1 mM of
melatonin reduced the viability of MCF-7 and MDA-MB-231 cells (p < .05). This treatment also decreased both gene and protein
expression of HIF-1α and VEGF-A under hypoxic conditions (p < .05). Among the proteins evaluated by protein array, melatonin
treatment during hypoxia reduced VEGF-C, VEGFR receptors (VEGFR2 and VEGFR3), matrix metalloproteinase 9 (MMP9) and
Angiogenin in MCF-7 cells. In MDA-MB-231 cells, a significant decrease was observed in VEGFR2, epidermal growth factor receptor
(EGFR) and Angiogenin (p < .05). Taken together, these results showed that melatonin acts in the regulation of angiogenic factors in
breast tumor cells and suggests an anti-angiogenic activity, particularly under hypoxic conditions.
Keywords: Angiogenesis, breast neoplasms, cell hypoxia, cell line, gene expression, melatonin, vascular endothelial growth factors.
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