title: Transplant drugs affect the expression of phase II and antioxidant enzymes in human carcinoma cells HepG2 but not in primary cultures of human hepatocytes: In vitro comparative study.
abstract: BACKGROUND
  We carried out a test whether or not transplant drugs such as cyclosporine A, Rapamycin (Sirolimus), Tacrolimus, Everolimus and Mycophenolate mofetil affects the expression of phase II enzymes comprising of UDP-glucuronosyltransferases (UGTs) and glutathione-S-transferases (GSTs), and antioxidant enzymes that consist of glutathione reductase (GSR), glutathione peroxidase 1 (GPX1) and heme-oxygenase 1 (HMOX1).
  
  
  METHODS
  Experiments were performed in primary cultures of human hepatocytes and in human hepatocarcinoma HepG2 cells, the models of metabolically competent and incompetent cells, respectively. We used quantitative real-time PCR.
  
  
  RESULTS
  We found that none of the tested compounds affected the expression of investigated genes in human hepatocytes. On the other hand, Mycophenolate mofetil induced GPX1 mRNA, although it suppressed mRNA level of UGT1A4/1A9/2B7/2B10, GSTA1/O1/T1, GSR and HMOX1 in HepG2 cells.
  
  
  CONCLUSIONS
  We showed that the tested transplant drugs have no effect on the expression of selected phase II and antioxidant enzymes in human hepatocytes. Nevertheless, the experiments carried out in two common and frequently used in vitro cellular models, we emphasize that finding based solely on carcinoma cells must be taken with caution when transposing to in vivo situations.
authors.affiliation: Department of Cell Biology and Genetics, Faculty of Science, Palacky University, Olomouc, Czech Republic. Electronic address: radim.vrzal@email.cz.
authors.forename: Radim
authors.initials: R
authors.lastname: Vrzal
authors.affiliation: Department of Cell Biology and Genetics, Faculty of Science, Palacky University, Olomouc, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Illes
authors.affiliation: Department of Cell Biology and Genetics, Faculty of Science, Palacky University, Olomouc, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Dvorak
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D014453:Glucuronosyltransferase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; D005980:Glutathione Reductase; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human
keywords: GPX1; Human hepatocytes; Mycophenolate mofetil; UGT1A