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

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 potential Pi-Alkyl interactions, but not conventional hydrogen bonds. The pharmacophore model indicated the aromatic ring B, hydrophobic groups and hydrogen bond acceptors may play critical role in the potency of flavonoids inhibition on BCRP. Thus, our findings would provide helpful information for predicting the potential risks of flavonoid-containing food/herb-drug interactions in humans.

• Publication year

  2019

• Venue

  Toxicology in Vitro

• Publication date

  2019-12-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.tiv.2019.104642PMID 31493543
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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