title: Pharmacologic concentrations of ascorbic acid cause diverse influence on differential expressions of angiogenic chemokine genes in different hepatocellular carcinoma cell lines.
abstract: This study was to investigate whether ascorbic acid (AA) at pharmacologic concentration became prooxidant and had the potential to influence the expressions of angiogenic and angiostatic chemokine genes in hepatocellular carcinoma (HCC) cell lines. Influence of low (1 mM) and high (30 mM) pharmacologic concentrations of AA on two HCC cell lines (cell line A, HCC24/KMUH; cell line B, HCC38/KMUH) were studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Three angiogenic genes (CCL2, CXCL6, IL8), one angiostatic gene (CXCL10) and two genes related to oxidative stress (SOD2, VNN3) were selected for quantitative RT-PCR study. Both low and high pharmacologic concentrations of AA up-regulated CCL2, CXCL6, IL8, SOD2 and VNN3 genes in cell line A, but down-regulated CCL2 and IL8 genes in cell line B. CXCL6 gene in cell line B was down-regulated by high pharmacologic concentration of AA. CXCL10 gene was up-regulated by low pharmacologic concentration of AA, but was down-regulated by high pharmacologic concentration of AA in both cell lines. Low pharmacologic concentration of AA up-regulated VNN3 gene and high pharmacologic concentration of AA up-regulated SOD2 gene in cell line B. These results indicate that pharmacologic concentration of AA becomes prooxidant to HCC cells and has diverse influence on differential expressions of angiogenic chemokine genes in different HCC cell lines. Differential expressions of CXCL10 gene are determined by the concentrations of AA used. Clinical application of AA in patients with HCC should consider these effects.
authors.affiliation: Division of Hepatobiliary Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, No. 100 Tzyou 1(st) Road, Kaohsiung 807, Taiwan.
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10 / Q000187:drug effects / Q000235:genetics; D018925:Chemokines / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D054357:Chemokine CXCL10; D018925:Chemokines; D017382:Reactive Oxygen Species; D001205:Ascorbic Acid