Evaluation of inhibitory effects of flavonoids on breast cancer resistance protein (BCRP): From library screening to biological evaluation to structure-activity relationship.

Evaluation of inhibitory effects of flavonoids on breast cancer resistance protein (BCRP): From library screening to biological evaluation to structure-activity relationship. Toxicol In Vitro. 2019 Sep 04;:104642 Authors: Fan X, Bai J, Zhao S, Hu M, Sun Y, Wang B, Ji M, Jin J, Wang X, Hu J, Li Y Abstract Flavonoids are a group of polyphenols ubiquitously present in vegetables, fruits and herbal products, despite various known pharmacological activities, few researches have been done about the interaction of flavonoids with breast cancer resistance protein (BCRP). The present study was designed to investigate the inhibitory effects of 99 flavonoids on BCRP in vitro and in vivo and to clarify structure-activity relationships of flavonoids with BCRP. Eleven flavonoids, including amentoflavone, apigenin, biochanin A, chrysin, diosimin, genkwanin, hypericin, kaempferol, kaempferide, licochalcone A and naringenin, exhibited significant inhibition (>50%) on BCRP in BCRP-MDCKII cells, which reduced the BCRP-mediated efflux of doxorubicin and temozolomide, accordingly increased their cytotoxicity. In addition, co-administration of mitoxantrone with the 11 flavonoids increased the AUC0-t of mitoxantrone in different extents in rats. Among them, chrysin increased the AUC0-t most significantly, by 81.97%. Molecular docking analysis elucidated the inhibition of flavonoids on BCRP might be associated with Pi-Pi stacked interactions and/or poten...
Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research