title: Upregulation of energy metabolism-related, p53-target TIGAR and SCO2 in HuH-7 cells with p53 mutation by geranylgeranoic acid treatment.
abstract: Metabolic alternation in cancer cells is one of the most common characteristics that distinguish malignant cells from normal cells. Many studies have explained the Warburg hypothesis that cancer cells obtain more energy from aerobic glycolysis than mitochondrial respiration. Here, we show that a branched-chain C-20 polyunsaturated fatty acid, geranylgeranoic acid (GGA), induces upregulation of the cellular protein levels of TP53-induced glycolysis and apoptosis regulator (TIGAR) and synthesis of cytochrome c oxidase 2 (SCO2) in human hepatoma-derived HuH-7cells harboring the mutant TP53 gene, suggesting that GGA may shift an energetic state of the tumor cells from aerobic glycolysis to mitochondrial respiration. In addition, UPLC/TOF/MS-based metabolomics analysis supported the GGA-induced energetic shift, as it revealed that GGA induced a time-dependent increase in the cellular contents of fructose 6-phosphate and decrease of fructose 1,6-diphosphate. Furthermore, metabolomics analysis revealed that GGA rapidly induced spermine accumulation with slight decrease of spermidine. Taken together, the present study strongly suggests that GGA may shift HuH-7 cells from aerobic glycolysis to mitochondrial respiration through the immediate upregulation of TIGAR and SCO2 protein levels.
authors.affiliation: Molecular and Cellular Biology, Graduate School of Human Health Science, University of Nagasaki.
authors.forename: Chieko
authors.initials: C
authors.lastname: Iwao
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Shidoji
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005635:Fructosediphosphates / Q000378:metabolism; D005636:Fructosephosphates / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism; D055432:Metabolomics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones; D015999:Multivariate Analysis; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D004224:Diterpenes; D005231:Fatty Acids, Unsaturated; D005635:Fructosediphosphates; D005636:Fructosephosphates; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C400285:SCO2 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C027618:fructose-6-phosphate; C040155:geranylgeranic acid; C007702:farnesoic acid; C017338:geranylgeraniol; D010744:Phosphoric Monoester Hydrolases; C512708:TIGAR protein, human; C029063:fructose-1,6-diphosphate