Modulatory actions of o -coumaric acid on carcinogen-activating cytochrome P450 isozymes and the potential for drug interactions in human hepatocarcinoma cells ∗
Autor: | Şen, Alaattin, Terzioglu, Gülsüm, Atmaca, Pelin, Çelik, Gurbet, Özgün, Özden, Arslan, Şevki |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Conference Paper
Western blotting Substrate Specificity Activation Metabolic Carcinogen activation Cytochrome P-450 Enzyme System dose response protein cleavage cytochrome P450 (CYP) genetics Drug Interactions HepG2 cells antineoplastic agent cytochrome P450 3A4 cytochrome P450 2C9 messenger RNA Liver Neoplasms Hep G2 Cells xenobiotic metabolism carcinogen EC50 Isoenzymes EC10 cytotoxicity metabolic activation coumaric acid cytochrome P450 1A2 isoenzyme Carcinoma Hepatocellular Coumaric Acids cytochrome P450 enzymology effective concentration Antineoplastic Agents densitometry reverse transcription polymerase chain reaction EC25 Humans controlled study human RNA Messenger enzyme specificity protein expression cell viability HepG2 cell line drug interaction Dose-Response Relationship Drug human cell eye diseases Carcinogens cytochrome P450 2E1 pathology metabolism |
Popis: | Context: 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. Materials and 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 7.39mM, respectively. A sublethal dose of 5mM was used throughout this study. The CYP1A2 protein and mRNA levels were increased by 52 and 40% (p |
Databáze: | OpenAIRE |
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