The drug efflux transporter P-glycoprotein, which is encoded by MDR1 (ABCB1), plays important roles in drug absorption, distribution, and elimination. We previously reported that dietary polyphenols such as quercetin, curcumin, honokiol, magnolol, caffeic acid phenetyl ester (CAPE), xanthohumol, and anacardic acid inhibit P-glycoprotein-mediated drug transport. In the present study, we investigated the effects of polyphenols on the expression of P-glycoprotein using human intestinal epithelial LS174T cells and a reporter plasmid expressing 10.2 kbp of the upstream regulatory region of MDR1. Honokiol, magnolol, CAPE, xanthohumol, and anacardic acid activated the MDR1 promoter in LS174T cells, and the cellular uptake of rhodamine 123 and calcein-AM, fluorescent substrates of P-glycoprotein, decreased in polyphenol-treated LS174T cells. These results suggest that dietary natural polyphenols can induce the drug efflux transporter P-glycoprotein and have the potential to promote food–drug interactions.

• The antidepressants, sertraline, paroxetine, fluvoxamine, and duloxetine, induce toxicity in human placental BeWo cells. • Escitalopram, venlafaxine, and mirtazapine showed little effects on placental cell viability. • Sertraline induces reactive oxygen species production and increases the number of apoptotic cells.

This study examined the effects of microtubule-targeting anticancer drugs (paclitaxel, cabazitaxel, and eribulin) on the expression of drug efflux transporter P-glycoprotein, which is encoded by MDR1. Paclitaxel and eribulin induced MDR1 promoter activity in a concentration-dependent manner, while cabazitaxel had little effect in human intestinal epithelial LS174T cells. Overexpression of the nuclear receptor pregnane X receptor (PXR) gene (NR1I2) enhanced paclitaxel- and eribulin-induced MDR1 activation, but expression of the nuclear receptor co-repressor silencing mediator for retinoid and thyroid receptors (SMRT) gene (NCOR2) repressed MDR1 activation. Eribulin increased the mRNA and protein expression of P-glycoprotein in LS174T cells. Cellular uptake of rhodamine 123 and calcein-acetoxymethyl ester (calcein-AM), P-glycoprotein substrates, decreased in paclitaxel- or eribulin-treated LS174T cells. Eribulin also increased MDR1 promoter activity in human breast cancer MCF7 cells. The results suggest that the microtubule-targeting anticancer drug eribulin can induce the drug efflux transporter P-glycoprotein via PXR in human intestinal and breast cancer cells and thus influence the efficacy of anticancer drugs.

Organic anion transporter 1 (OAT1, SLC22A6) and 3 (OAT3, SLC22A8) are multispecific drug transporters highly expressed on the basolateral membranes of the renal proximal tubules. OAT1 and OAT3 mediate the tubular secretion of clinically significant drugs; thus, they influence the pharmacokinetics of drugs and further determine their efficacy and toxicity. OAT1 and OAT3 are also the target of drug–drug interactions. In this study, we examined the effects of the tea catechin (−)-epigallocatechin-3-gallate (EGCG) on human (h) and rat (r) OAT1 and OAT3 using the fluorescent organic anion 6-carboxyfluorescein (6-CF) and hOAT1-, hOAT3-, rOat1-, or rOat3-expressing HEK293 cells and on renal elimination of 6-CF in rats. 6-CF is transported by hOAT1, hOAT3, rOat1, and rOat3. 6-CF is urinary excreted by Oats in rats. EGCG, a dominant catechin in green tea leaf, inhibits human and rat OAT1 and OAT3 and reduces the renal elimination of 6-CF in rats. Our findings are useful for the assessment of food–drug interactions mediated by renal OATs.