Effect of Vitamin K-Mediated PXR Activation on Drug-Metabolizing Gene Expression in Human Intestinal Carcinoma LS180 Cell Line
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....
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MDPI AG
2021-05-01
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| author | Halima Sultana Ayaka Kato Ai Ohashi Rie Takashima Tomoko Katsurai Shoko Sato Masafumi Monma Yusuke Ohsaki Tomoko Goto Michio Komai Hitoshi Shirakawa |
| author_facet | Halima Sultana Ayaka Kato Ai Ohashi Rie Takashima Tomoko Katsurai Shoko Sato Masafumi Monma Yusuke Ohsaki Tomoko Goto Michio Komai Hitoshi Shirakawa |
| author_sort | Halima Sultana |
| collection | DOAJ |
| description | 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 menaquinone 4 (MK-4), along with other vitamin Ks, including vitamin K<sub>1</sub>, has the potential to induce <i>MDR1</i> and <i>CYP3A4</i> gene expression. We showed that PXR knockdown reversed MK-4-mediated stimulation of these genes, indicating the involvement of PXR in this effect. In addition, we showed that the expression of <i>MDR1</i> and <i>CYP3A4</i> 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. |
| first_indexed | 2024-03-10T11:18:23Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T11:18:23Z |
| publishDate | 2021-05-01 |
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| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-b99e125f747f4ba2ac0685d85765ea712023-11-21T20:14:12ZengMDPI AGNutrients2072-66432021-05-01135170910.3390/nu13051709Effect of Vitamin K-Mediated PXR Activation on Drug-Metabolizing Gene Expression in Human Intestinal Carcinoma LS180 Cell LineHalima Sultana0Ayaka Kato1Ai Ohashi2Rie Takashima3Tomoko Katsurai4Shoko Sato5Masafumi Monma6Yusuke Ohsaki7Tomoko Goto8Michio Komai9Hitoshi Shirakawa10Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, JapanLaboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, JapanLaboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, JapanLaboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, JapanLaboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, JapanLaboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, JapanLaboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, JapanLaboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, JapanLaboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, JapanLaboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, JapanLaboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza Aoba, Aoba-ku, Sendai 980-8572, JapanThe 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 menaquinone 4 (MK-4), along with other vitamin Ks, including vitamin K<sub>1</sub>, has the potential to induce <i>MDR1</i> and <i>CYP3A4</i> gene expression. We showed that PXR knockdown reversed MK-4-mediated stimulation of these genes, indicating the involvement of PXR in this effect. In addition, we showed that the expression of <i>MDR1</i> and <i>CYP3A4</i> 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.https://www.mdpi.com/2072-6643/13/5/1709pregnane X receptorvitamin Kisoprenoidsdrug–nutrient interaction |
| spellingShingle | Halima Sultana Ayaka Kato Ai Ohashi Rie Takashima Tomoko Katsurai Shoko Sato Masafumi Monma Yusuke Ohsaki Tomoko Goto Michio Komai Hitoshi Shirakawa Effect of Vitamin K-Mediated PXR Activation on Drug-Metabolizing Gene Expression in Human Intestinal Carcinoma LS180 Cell Line Nutrients pregnane X receptor vitamin K isoprenoids drug–nutrient interaction |
| title | Effect of Vitamin K-Mediated PXR Activation on Drug-Metabolizing Gene Expression in Human Intestinal Carcinoma LS180 Cell Line |
| title_full | Effect of Vitamin K-Mediated PXR Activation on Drug-Metabolizing Gene Expression in Human Intestinal Carcinoma LS180 Cell Line |
| title_fullStr | Effect of Vitamin K-Mediated PXR Activation on Drug-Metabolizing Gene Expression in Human Intestinal Carcinoma LS180 Cell Line |
| title_full_unstemmed | Effect of Vitamin K-Mediated PXR Activation on Drug-Metabolizing Gene Expression in Human Intestinal Carcinoma LS180 Cell Line |
| title_short | Effect of Vitamin K-Mediated PXR Activation on Drug-Metabolizing Gene Expression in Human Intestinal Carcinoma LS180 Cell Line |
| title_sort | effect of vitamin k mediated pxr activation on drug metabolizing gene expression in human intestinal carcinoma ls180 cell line |
| topic | pregnane X receptor vitamin K isoprenoids drug–nutrient interaction |
| url | https://www.mdpi.com/2072-6643/13/5/1709 |
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