Genistein Affects Expression of Cytochrome P450 (CYP450) Genes in Hepatocellular Carcinoma (HEPG2/C3A) Cell Line

• Published in: Drug metabolism letters Vol. 12; no. 2; p. 138
• Main Authors: Lepri, Sandra R, Sartori, Daniele, Semprebon, Simone C, Baranoski, Adrivanio, Coatti, Giuliana C, Mantovani, Mario S
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 2018
• Subjects: Anticarcinogenic Agents - pharmacology; Biotransformation; Carcinoma, Hepatocellular - enzymology; Carcinoma, Hepatocellular - genetics; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Dose-Response Relationship, Drug; Gene Expression Regulation, Enzymologic - drug effects; Genistein - pharmacology; Hep G2 Cells; HT29 Cells; Humans; Liver Neoplasms - enzymology; Liver Neoplasms - genetics; Xenobiotics - metabolism; cytochrome P450; isoflavones; All-Trans-Retinoic Acid (ATRA); Genistein; hepatocellular carcinoma; xenobiotics metabolism
• ISSN: 1874-0758
• DOI: 10.2174/1872312812666180709150440

Genistein (5,7-Dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is the most abundant isoflavone in soybean, which has been associated with a lower risk of development of cancer and cardiovascular diseases. Of particular interest regarding cancer preventive properties of flavonoids is their interaction with cytochrome P450 enzymes (CYPs). However, contradictory data report the effect of genistein on expression of СYPs enzymes. The aim of this study was to investigate the effects of genistein on cytochrome P450 (CYP) gene expression levels in human hepatocellular carcinoma (HepG2/C3A) and colon adenocarcinoma (HT29) cells. Real-time RT-PCR was used to examine the expression of genes families involved in xenobiotic metabolism, such as CYP1 (CYP1A1, CYP1B1), CYP2 (CYP2E1, CYP2D6), CYP3 (CYP3A4); and of a family involved in the catabolism of the all-trans-retinoic acid (ATRA), CYP26 (CYP26A1, CYP26B1). RT-qPCR data analysis showed that after 12 h of exposure of HepG2/C3A cells to genistein (5 and 50 µM) there was an upregulation of CYP1A1 and CYP1B1 and downregulation of CYP2D6, CYP26A1 and CYP26B1 mRNA levels. There was no change in the mRNA levels of CYP P450 genes in HT29 cells. Our results suggest that treatment with genistein in non-toxic concentrations may impact the expression level of CYPs involved in the biotransformation of xenobiotics and drug metabolizing enzymes. Moreover, the downregulation of ATRA metabolism-related genes opens a new research path for the study of genistein as retinoic acid metabolism blocking agent for treating cancer and other pathologies.