Melatonin suppresses tumor progression by reducing angiogenesis stimulated by HIF-1 in a mouse tumor model.

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.
AuthorsKil-Jung Kim, Jae-Sun Choi, Insug Kang, Kyu-Won Kim, Chul-Ho Jeong, Joo-Won Jeong
JournalJournal of pineal research (J Pineal Res) Vol. 54 Issue 3 Pg. 264-70 (Apr 2013) ISSN: 1600-079X [Electronic] England
PMID22924616 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2012 John Wiley & Sons A/S.
Chemical References
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Melatonin
  • Animals
  • Cell Line, Tumor
  • Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors, biosynthesis, metabolism)
  • Kidney Neoplasms (blood supply, drug therapy, metabolism, pathology)
  • Male
  • Melatonin (pharmacology)
  • Mice
  • Mice, Inbred BALB C
  • Microvessels (drug effects, pathology)
  • Neovascularization, Pathologic (drug therapy, pathology)

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