title: The effect of indatraline on angiogenesis suppression through HIF-1α-mediated VEGF inhibition.
abstract: The present research reports a novel biological activity of indatraline, a compound clinically used as an antidepressant. We previously identified indatraline as an autophagy inducer. Autophagy is an intracellular catabolic pathway for degrading or recycling unnecessary organelles in response to cellular stress. Indatraline-mediated autophagy induction results from mTOR inhibition. The mTOR is a negative regulator of autophagy as well as a master regulator of angiogenesis. Angiogenesis defines the process by which new vessels are formed from pre-existing vascular tissues, providing nutrients to cancer cells, allowing rapid tumor progression. Accordingly, targeting angiogenesis to prevent cancer is an attractive therapeutic strategy. Here, we demonstrate that indatraline possibly acts to suppress tumor-mediated angiogenesis via downregulation of HIF-1α-mediated VEGF expression. The effects of indatraline on autophagy and angiogenesis could make it a potential drug candidate toward cancer treatment.
authors.affiliation: Chemical Genomics Global Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Chih-Na
authors.initials: CN
authors.lastname: Yen
authors.affiliation: Chemical Genomics Global Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Yoon Sun
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Chemical Genomics Global Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea. Electronic address: kwonhj@yonsei.ac.kr.
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D015687:Cell Hypoxia; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D015151:Immunoblotting; D007189:Indans / Q000737:chemistry / Q000494:pharmacology*; D008744:Methylamines / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007189:Indans; D008744:Methylamines; D042461:Vascular Endothelial Growth Factor A; C418119:indatraline
keywords: Angiogenesis; Anticancer; Autophagy; HIF-1α; mTOR