Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE), School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Biol Pharm Bull. 2010;33(2):255-9. doi: 10.1248/bpb.33.255.
The present study was conducted to investigate the functional and transcriptional modulation of P-glycoprotein (MDR-1) by several dietary ingredients (piperine, capsaicin, daidzein, genistein, sesamin, curcumin, taurine) in vinblastine-resistant colon carcinoma LS-180 cells (LS-180V cells). The amount of rhodamine 123 accumulated in LS-180V cells was significantly increased by capsaicin, piperine and sesamin, whereas it was significantly reduced by daidzein and genistein which stimulated the efflux of rhodamine 123. These results suggest that the P-glycoprotein-mediated efflux is inhibited by piperine, capsaicin and sesamin and stimulated by daidzein and genistein. The concurrent addition of piperine and capsaicin seemed to inhibit synergistically the P-glycoprotein-mediated efflux. Pretreatment with sesamin for 48 h caused a significant increase in MDR1 mRNA expression without a significant effect on the expression of P-glycoprotein or accumulation of rhodamine 123. Similar pretreatment with other ingredients had little effect on the expression of MDR1 mRNA or P-glycoprotein, suggesting that they do not cause transcriptional modulation of P-glycoprotein. Piperine, genistein and curcumin have been suggested to stimulate P-glycoprotein-mediated efflux without increasing P-glycoprotein expression. In LS-180V cells, significant increases in mRNA levels of multi-drug resistance associated protein 1 (MRP1) or MRP3 were observed on pretreatment with capsaicin, daidzein, piperine and sesamin. In conclusion, our results suggest that P-glycoprotein-mediated efflux is significantly affected by dietary ingredients. Also, capsaicin, daidzein, piperine and sesamin increased significantly the mRNA expression of MRP1 or MRP3. Thus, the present study provides further evidence that repeated exposure to dietary ingredients can cause drug-food interactions by affecting the function and mRNA expression of intestinal transporters such as P-glycoprotein.
本研究旨在探讨几种膳食成分（胡椒碱、辣椒素、大豆苷元、染料木黄酮、芝麻素、姜黄素、牛磺酸）对长春新碱耐药结肠癌细胞（LS-180V 细胞）中 P-糖蛋白（MDR-1）的功能和转录调节作用。LS-180V 细胞中累积的罗丹明 123 量明显增加了辣椒素、胡椒碱和芝麻素，而大豆苷元和染料木黄酮则显著减少了罗丹明 123 的流出，这表明 P-糖蛋白介导的外排被胡椒碱、辣椒素和芝麻素抑制，被大豆苷元和染料木黄酮刺激。胡椒碱和辣椒素的协同抑制作用似乎协同抑制了 P-糖蛋白介导的外排。芝麻素预处理 48 小时导致 MDR1 mRNA 表达显著增加，而对 P-糖蛋白表达或罗丹明 123 积累没有显著影响。其他成分的类似预处理对 MDR1 mRNA 或 P-糖蛋白的表达影响不大，表明它们不会引起 P-糖蛋白的转录调节。胡椒碱、染料木黄酮和姜黄素被认为刺激 P-糖蛋白介导的外排而不增加 P-糖蛋白的表达。在 LS-180V 细胞中，用辣椒素、大豆苷元、胡椒碱和芝麻素预处理后，多药耐药相关蛋白 1（MRP1）或 MRP3 的 mRNA 水平显著增加。总之，我们的研究结果表明，膳食成分显著影响 P-糖蛋白介导的外排。此外，辣椒素、大豆苷元、胡椒碱和芝麻素显著增加了 MRP1 或 MRP3 的 mRNA 表达。因此，本研究进一步证明，反复接触膳食成分可能通过影响肠道转运蛋白（如 P-糖蛋白）的功能和 mRNA 表达，导致药物-食物相互作用。
