title: Melatonin suppresses tumor progression by reducing angiogenesis stimulated by HIF-1 in a mouse tumor model.
abstract: The sustained expansion of a tumor mass requires new blood vessel formation to provide rapidly proliferating tumor cells with an adequate supply of oxygen and nutrients. Hypoxia-inducible factor-1 (HIF-1) plays an essential role in tumor angiogenesis and growth by regulating the transcription of genes in response to hypoxic stress. This study was designed to investigate the effects of melatonin on tumor growth and angiogenesis, as well as the mechanism underlying the antitumor activities of melatonin. In this study, we show that the administration of melatonin inhibits tumor growth and blocks tumor angiogenesis in mice. Moreover, melatonin diminished the expression of the HIF-1α protein within the tumor mass during tumorigenesis. Our findings suggest that melatonin is a promising anti-angiogenic therapeutic agent targeting HIF-1α in cancer. Considering that HIF-1α is overexpressed in a majority of human cancers, melatonin could offer a potent therapeutic agent for cancer.
authors.affiliation: Department of Biomedical Science, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Kil-Jung
authors.initials: KJ
authors.lastname: Kim
authors.forename: Jae-Sun
authors.initials: JS
authors.lastname: Choi
authors.forename: Insug
authors.initials: I
authors.lastname: Kang
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Jeong
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Jeong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008550:Melatonin