title: Modulatory actions of o-coumaric acid on carcinogen-activating cytochrome P450 isozymes and the potential for drug interactions in human hepatocarcinoma cells.
abstract: BACKGROUND
  Although humans are exposed to o-coumaric acid (OCA) in their diet, there is no available literature related to drug interaction and the carcinogen-activating potential of OCA in the HepG2 cell line.
  
  
  OBJECTIVE
  This study was undertaken to determine the effects of OCA on the cytochrome P450 (CYP) 1A2, CYP2E1, CYP2C9, and CYP3A4 enzymes, which are primarily involved in carcinogen and drug metabolism.
  
  
  METHODS
  The cytotoxicity of OCA in HepG2 cells was investigated by measuring the cleavage of WST-1. The protein and mRNA levels of CYPs were determined by western blotting and RT-PCR, respectively.
  
  
  RESULTS
  The EC10, EC25, and EC50 values of OCA were calculated to be 1.84, 3.91 and 7.39 mM, respectively. A sublethal dose of 5 mM was used throughout this study. The CYP1A2 protein and mRNA levels were increased by 52 and 40% (p < 0.05), as were the CYP2E1 levels by 225 and 424%, respectively (p < 0.05). However, OCA treatment caused 52 and 60% decreases in the levels of CYP3A4 protein and mRNA (p < 0.05), respectively. In contrast to CYP3A4, the CYP2C9 protein and mRNA levels increased by 110 and 130%, respectively.
  
  
  CONCLUSIONS
  Co-administration of OCA with some drugs may lead to undesirable food-drug interactions due to modulatory effects on CYP isozymes involved in drug metabolism. Moreover, exposure to OCA may cause an increase in carcinogenicity and toxicity due to the induction of the CYP isozymes involved in chemical carcinogenesis. Therefore, serious precautions should be taken when using OCA as a supplement.
authors.affiliation: Department of Biology, Pamukkale University , Kinikli Campus, Denizli , Turkey.
authors.forename: Alaattin
authors.initials: A
authors.lastname: Sen
authors.forename: Gulsum
authors.initials: G
authors.lastname: Terzioglu
authors.forename: Pelin
authors.initials: P
authors.lastname: Atmaca
authors.forename: Gurbet
authors.initials: G
authors.lastname: Celik
authors.forename: Ozden
authors.initials: O
authors.lastname: Ozgun
authors.forename: Sevki
authors.initials: S
authors.lastname: Arslan
mesh_terms: D065767:Activation, Metabolic; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D003373:Coumaric Acids / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D056945:Hep G2 Cells; D006801:Humans; D007527:Isoenzymes; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D000970:Antineoplastic Agents; D002273:Carcinogens; D003373:Coumaric Acids; D007527:Isoenzymes; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System
keywords: Carcinogen activation; HepG2 cells; cytochrome P450 (CYP)