Fucoxanthin attenuates rifampin-induced cytochrome P450 3A4 (CYP3A4) and multiple drug resistance 1 (MDR1) gene expression through pregnane X receptor (PXR)-mediated pathways in human hepatoma HepG2 and colon adenocarcinoma LS174T cells.
Up-regulation of MDR1, which encodes for P-glycoprotein, was confirmed using real-time RT-PCR and Western analysis in hepatocytes as well as in human colon adenocarcinoma cell line (LS-180) and the induction was dose-dependent.
To examine such a hypothesis, the effect of DEHP on SXR-mediated transcription of the MDR1 gene was studied in the human colon adenocarcinoma-derived cell line, LS174T cells, which endogenously express SXR.
The 285-fold doxorubicin-resistant colon adenocarcinoma subline, LoVo/DR5, was found to overexpress the mRNA for P-glycoprotein without the concomitant requirement of MDR1 gene amplification, suggesting that relatively high levels of P-glycoprotein mediated multiple drug resistance may occur by transcriptional activation of the gene.