Identification of novel dietary phytochemicals inhibiting the efflux transporter breast cancer resistance protein (BCRP/ABCG2)

Breast cancer resistance protein (BCRP/ABCG2) plays an important role in determining the absorption and disposition of consumed xenobiotics including various drugs and dietary phytochemicals and is also one of the prominent efflux transporters involved in multidrug resistance (MDR). In this study, we have investigated the interactions between ABCG2 and 56 naturally-occurring phytochemicals including phenolic acids, flavonoids, triterpenes and other common dietary phytochemicals, as well as two non plant-based compounds (hippuric acid and propyl gallate) using cell- and membrane-based transport inhibition assays. Of the non-flavonoid phytochemicals tested, berberine, celastrol, ellagic acid, limonin, oleanolic acid, propyl gallate, sinapic acid and ursolic acid demonstrated significant inhibition of ABCG2-mediated transport. Chrysoeriol, laricitrin, myricetin 3′,4′,5′-trimethylether, pinocembrin, quercitrin, tamarixetin, tricetin and tricetin 3′,4′,5′-trimethylether were also identified as novel flavonoid ABCG2 inhibitors. The identified inhibitory activity of dietary phytochemicals on ABCG2 provides a framework for further investigation of ABCG2-modulated phytochemical bioavailability, MDR, and possible food–drug interactions.

► We examined ABCG2-inhibitory activity of dietary phytochemicals.
► Novel non-flavonoid inhibitors: berberine, celastrol, ellagic acid, limonin, oleanolic acid, propyl gallate, sinapic acid, ursolic acid.
► Novel flavonoid inhibitors: chrysoeriol, laricitrin, myricetin 3′,4′,5′ trimethylether, pinocembrin, quercitrin, tamarixetin, tricetin, tricetin 3′,4′,5′ trimethylether.