title: Time Course Effect of R-Alpha-Lipoic Acid on Cellular Metabolomics in Cultured Hepatoma Cells.
abstract: Alpha-lipoic acid (LA) is a powerful antioxidant. LA has two enantiomers, R(+)-LA (R-LA) and S(-)-LA (S-LA). Of these, R-LA is naturally occurring and an essential cofactor in energy metabolism. R-LA treatment has been reported to affect glucose metabolism in rat hepatoma cells. This study analyzed the time course of metabolite levels in LA-treated cultured H4IIEC3 rat hepatoma cells, including a specific evaluation of the effect of R-LA and the enantioselectivity of LA. Principal component analysis showed that this experiment was well designed to observe enantioselectivity. R-LA treatment was found to inhibit the glycolysis and Thr-Gly-Ser pathways, as well as lactic acid production, leading to the inhibition of gluconeogenesis in starved H4IIEC3 cells. This study may provide mechanistic insight into how R-LA induces apoptosis in hepatoma cells.
authors.affiliation: 1 Graduate School of Medicine, Kobe University , Kobe, Japan .
authors.forename: Naoko
authors.initials: N
authors.lastname: Ikuta
authors.affiliation: 2 College of Science and Engineering, Kanazawa University , Kanazawa, Japan .
authors.forename: Keita
authors.initials: K
authors.lastname: Chikamoto
authors.affiliation: 2 College of Science and Engineering, Kanazawa University , Kanazawa, Japan .
authors.forename: Yuya
authors.initials: Y
authors.lastname: Asano
authors.affiliation: 2 College of Science and Engineering, Kanazawa University , Kanazawa, Japan .
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yasui
authors.affiliation: 2 College of Science and Engineering, Kanazawa University , Kanazawa, Japan .
authors.forename: Haruka
authors.initials: H
authors.lastname: Yokokawa
authors.affiliation: 3 CycloChem Bio Co., Ltd. , Kobe, Japan .
authors.forename: Keiji
authors.initials: K
authors.lastname: Terao
authors.affiliation: 4 Institute of Human Nutrition and Food Science, University of Kiel , Kiel, Germany .
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
authors.affiliation: 2 College of Science and Engineering, Kanazawa University , Kanazawa, Japan .
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsugo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D055432:Metabolomics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013237:Stereoisomerism; D008063:Thioctic Acid / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D008063:Thioctic Acid; D005947:Glucose
keywords: H4IIEC3; amino acids; enantioselectivity; glyconeogenesis; hepatoma cells; lipoic acid; metabolomics