Effect of vitamin k-mediated pxr activation on drug-metabolizing gene expression in human intestinal carcinoma ls180 cell line

Halima Sultana, Ayaka Kato, Ai Ohashi, Rie Takashima, Tomoko Katsurai, Shoko Sato, Masafumi Monma, Yusuke Ohsaki, Tomoko Goto, Michio Komai, Hitoshi Shirakawa

Research output: Contribution to journalArticlepeer-review

Abstract

The pregnane X receptor (PXR) is the key regulator of our defense mechanism against foreign substances such as drugs, dietary nutrients, or environmental pollutants. Because of increased health consciousness, the use of dietary supplements has gradually increased, and most of them can activate PXR. Therefore, an analysis of the interaction between drugs and nutrients is important because altered levels of drug-metabolizing enzymes or transporters can remarkably affect the efficiency of a co-administered drug. In the present study, we analyzed the effect of vitamin K-mediated PXR activation on drug metabolism-related gene expression in intestine-derived LS180 cells via gene expression studies and western blotting analyses. We demonstrated that menaqui-none 4 (MK-4), along with other vitamin Ks, including vitamin K1, has the potential to induce MDR1 and CYP3A4 gene expression. We showed that PXR knockdown reversed MK-4-mediated stimula-tion of these genes, indicating the involvement of PXR in this effect. In addition, we showed that the expression of MDR1 and CYP3A4 genes increased synergistically after 24 h of rifampicin and MK-4 co-treatment. Our study thus elucidates the importance of drug–nutrient interaction mediated via PXR.

Original languageEnglish
Article number1709
JournalNutrients
Volume13
Issue number5
DOIs
Publication statusPublished - 2021 May

Keywords

  • Drug–nutrient interaction
  • Isoprenoids
  • Pregnane X receptor
  • Vitamin K

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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