title: Modulatory effects of rutin on the expression of cytochrome P450s and antioxidant enzymes in human hepatoma cells.
abstract: Expression of a drug and xenobiotic metabolizing enzymes, cytochrome P450s (CYPs), and antioxidant enzymes can be modulated by various factors. The flavonoid rutin was investigated for its anti-carcinogen and protective effects as well as modulatory action on CYPs and phase II enzymes in human hepatocellular carcinoma cells. Rutin inhibited proliferation of HEPG2 cells in a dose-dependent manner with the IC50 value of 52.7 μmol L-1 and invasion of HEPG2 cells (21.6 %, p = 0.0018) and colony formation of those invaded cells (57.4 %, p < 0.0001). Rutin treatment also significantly increased early/late-stage apoptosis in HEPG2 cells (28.9 %, p < 0.001). Treatment by rutin significantly inhibited protein expressions of cytochrome P450-dependent CYP3A4 (75.3 %, p < 0.0001), elevated CYP1A1 enzymes (1.7-fold, p = 0.0084) and increased protein expressions of antioxidant and phase II reaction catalyzing enzymes, NQO1 (2.42-fold, p < 0.0001) and GSTP1 (2.03-fold, p < 0.0001). Besides, rutin treatment significantly inhibited mRNA expression of CYP3A4 (73.2 %, p=0.0014). Also, CYP1A1, NQO1 and GSTP1 mRNA expressions were significantly increased 2.77-fold (p = 0.029), 4.85- fold (p = 0.0051) and 9.84-fold (p < 0.0001), respectively.
authors.forename: Sedar
authors.initials: S
authors.lastname: Karakurt
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D019363:Cytochrome P-450 CYP1A1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D004794:Enzyme Repression / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D051549:Glutathione S-Transferase pi / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012431:Rutin / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D009363:Neoplasm Proteins; D012431:Rutin; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi