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

Authors

  • Kil-Jung Kim,

    1. Department of Biomedical Science, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea
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    • These authors equally contributed to this work.
  • Jae-Sun Choi,

    1. Department of Biomedical Science, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea
    2. Department of Anatomy and Neurobiology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea
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    • These authors equally contributed to this work.
  • Insug Kang,

    1. Department of Biomedical Science, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea
    2. Department of Biochemistry and Molecular Biology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea
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  • Kyu-Won Kim,

    1. NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea
    2. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea
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  • Chul-Ho Jeong,

    Corresponding author
    1. College of Pharmacy, Keimyung University, Daegu, Korea
    • Department of Biomedical Science, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea
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  • Joo-Won Jeong

    Corresponding author
    1. Department of Anatomy and Neurobiology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea
    • Department of Biomedical Science, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea
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Address reprint requests to Joo-Won Jeong, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.

E-mail: jjeong@khu.ac;

krChul-Ho Jeong, College of Pharmacy, Keimyung University, Daegu, 704-701, Korea.

E-mail: chjeong75@kmu.ac.kr

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.

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