title: Conjugated linoleic acids inhibit hypoxia inducible factor-1α stabilization under hypoxic condition in human hepatocellular carcinoma cells.
abstract: The anti-cancer effects of various fatty acids are drawing a lot of attention. To determine whether different fatty acids affect the hypoxic response of liver cancer cells, we examined the effects of various fatty acids on the stabilization of the hypoxia-inducible factor (HIF)-1α protein in the HepG2 human hepatocellular carcinoma (HCC) cell line under condition containing 1% O(2). Of the fatty acids examined, only 9cis, 11trans (c9, t11)-conjugated linoleic acid (CLA) and 10trans, 12cis (t10, c12)-CLA inhibited hypoxia-induced HIF-1α stabilization. In addition, HIF-1α prolyl hydroxylase or proteasome inhibition abrogated the effects of c9, t11- and t10, c12-CLA. Moreover, c9, t11- and t10, c12-CLA significantly inhibited cell proliferation and induced apoptotic cell death under hypoxia. This is the first study showing that c9, t11- and t10, c12-CLA inhibit the hypoxic response in HCC cells.
authors.affiliation: Division of Food Science and Nutrition, Department of Biochemistry and Applied Biosciences, University of Miyazaki, Miyazaki, Japan. myamasaki@cc.miyazaki-u.ac.jp
authors.forename: Masao
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Taku
authors.initials: T
authors.lastname: Nagatomo
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Yuri
authors.initials: Y
authors.lastname: Ikeho
authors.forename: Emiko
authors.initials: E
authors.lastname: Kato
authors.forename: Kei
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakakibara
authors.forename: Masahito
authors.initials: M
authors.lastname: Suiko
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nishiyama
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D044243:Linoleic Acids, Conjugated / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D055550:Protein Stability / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D044243:Linoleic Acids, Conjugated