title: Melatonin modulates the expression of VEGF and HIF-1 alpha induced by CoCl2 in cultured cancer cells.
abstract: Melatonin is an important natural oncostatic agent. At present there are no data available as to its possible influence on tumor angiogenesis, which is a major biological mechanism responsible for tumor growth and dissemination. It is well known that vascular endothelial growth factor (VEGF) is crucial to a solid tumor's higher vascularization and development. To investigate the possible influence of melatonin on angiogenesis, we studied the effect of melatonin on endogenous VEGF expression in three human cancer cell lines (PANC-1, HeLa and A549 cells). In this study, we report that physiologic concentrations of melatonin have no obvious impact on the VEGF expression, whereas pharmacologic concentrations of melatonin suppress the VEGF mRNA and protein levels induced by hypoxia mimetic cobalt chloride (CoCl(2)). Melatonin also decreases hypoxia-inducible factor (HIF)-1alpha protein levels, suggesting a role for transcription factor HIF-1 in the suppression of VEGF expression. The effect of pharmacologic concentrations of melatonin on VEGF and HIF-1alpha under normoxia is uncertain, which indicates that the regulatory mechanisms of VEGF in the absence or presence of CoCl(2) are different and other or additional transcription factors may be involved. Taken together, our data show that melatonin in high concentrations markedly reduces the expression of endogenous VEGF and HIF-1alpha induced by CoCl(2) in cultured cancer cells.
authors.affiliation: Institute of Microcirculation, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.forename: Peilin
authors.initials: P
authors.lastname: Cui
authors.forename: Minghua
authors.initials: M
authors.lastname: Yu
authors.forename: Jianqun
authors.initials: J
authors.lastname: Han
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Xiu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000502:physiology*; D045744:Cell Line, Tumor; D003035:Cobalt / Q000494:pharmacology*; D015536:Down-Regulation / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008550:Melatonin / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; C018021:cobaltous chloride; D008550:Melatonin