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

[ Vol. 12 , Issue. 2 ]

Author(s):

Sandra R. Lepri, Daniele Sartori, Simone C. Semprebon*, Adrivanio Baranoski, Giuliana C. Coatti and Mario S. Mantovani   Pages 138 - 144 ( 7 )

Abstract:


Background: 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.

Objective: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Keywords:

Genistein, isoflavones, cytochrome P450, All-Trans-Retinoic Acid (ATRA), xenobiotics metabolism, hepatocellular carcinoma.

Affiliation:

Departamento de Biologia Geral, Universidade Estadual de Londrina (UEL), Londrina, Parana, Departamento de Bioquimica, Universidade Estadual de Londrina (UEL), Londrina, Parana, Departamento de Biologia Geral, Universidade Estadual de Londrina (UEL), Londrina, Parana, Departamento de Biologia Geral, Universidade Estadual de Londrina (UEL), Londrina, Parana, Instituto de Biociencias. Centro de Pesquisas sobre o Genoma Humano e Celulas-Tronco, Universidade de Sao Paulo (USP), Sao Paulo, Departamento de Biologia Geral, Universidade Estadual de Londrina (UEL), Londrina, Parana

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