Lepri Sandra R, Sartori Daniele, Semprebon Simone C, Baranoski Adrivanio, Coatti Giuliana C, Mantovani Mario S
Departamento de Biologia Geral, Universidade Estadual de Londrina (UEL), Londrina, Parana, Brazil.
Departamento de Bioquimica, Universidade Estadual de Londrina (UEL), Londrina, Parana, Brazil.
Drug Metab Lett. 2018;12(2):138-144. 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.
染料木黄酮（5,7 - 二羟基 - 3 -（4 - 羟基苯基）- 4H - 1 - 苯并吡喃 - 4 - 酮）是大豆中含量最丰富的异黄酮，它与降低癌症和心血管疾病的发病风险有关。黄酮类化合物的防癌特性中特别值得关注的是它们与细胞色素P450酶（CYPs）的相互作用。然而，关于染料木黄酮对CYPs酶表达的影响，数据存在矛盾。
本研究旨在探讨染料木黄酮对人肝癌（HepG2/C3A）和结肠腺癌（HT29）细胞中细胞色素P450（CYP）基因表达水平的影响。
采用实时逆转录 - 聚合酶链反应（Real - time RT - PCR）检测参与外源性物质代谢的基因家族的表达，如CYP1（CYP1A1、CYP1B1）、CYP2（CYP2E1、CYP2D6）、CYP3（CYP3A4）；以及参与全反式维甲酸（ATRA）分解代谢的基因家族CYP26（CYP26A1、CYP26B1）。
RT - qPCR数据分析表明，将HepG2/C3A细胞暴露于染料木黄酮（5和50 μM）12小时后，CYP1A1和CYP1B1上调，CYP2D6、CYP26A1和CYP26B1的mRNA水平下调。HT29细胞中CYP P450基因的mRNA水平没有变化。
我们的结果表明，无毒浓度的染料木黄酮处理可能会影响参与外源性物质生物转化和药物代谢酶的CYPs的表达水平。此外，ATRA代谢相关基因的下调为研究染料木黄酮作为治疗癌症和其他疾病的维甲酸代谢阻断剂开辟了新的研究途径。
