**5. Conclusions**

The in vitro and in vivo inhibitory potencies of quercetin against BCRP were examined focusing on functional and/or kinetic aspects. Quercetin significantly increased the cellular accumulation and associated cytotoxicity of mitoxantrone in HeLa cells in a concentration-dependent manner. The transcellular efflux of prazosin was significantly reduced in the presence of quercetin as observed in a bi-directional transport assay using MDCKII/BCRP cells. These modulations in BCRP activity were consistent with the in vivo results, where pretreatment with quercetin led to not very dramatically different but still significantly higher intestinal absorption of sulfasalazine compared to that in the control group. Collectively, these results provide evidence that quercetin acts as a potent inhibitor of BCRP both in vitro and in vivo. Considering the high dietary intake of quercetin as well as its consumption as a dietary supplement, careful attention should be paid to potential flavonoid–drug interactions.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/1999-4923/12/5/397/s1, Figure S1: mRNA expression levels of BCRP in HeLa, Caco-2, MCF-7 and SW620 cell lines using RT-PCR, Figure S2: Effect of 100 µM quercetin alone on the cell viability of HeLa cells.

**Author Contributions:** Conceptualization, H.-J.M. and Y.-K.S.; methodology, investigation and formal analysis, Y.-K.S., J.-H.Y., J.K.W., J.-H.K., K.-R.L., S.H.O. and H.-J.M.; resources, S.-J.C. and H.-J.M.; writing—original draft preparation and visualization, Y.-K.S., J.K.W. and H.-J.M.; writing—review and editing, S.-J.C. and H.-J.M.; supervision, S.-J.C. and H.-J.M; project administration, H.-J.M.; funding acquisition, H.-J.M. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2019R1F1A1058103).

**Conflicts of Interest:** The authors declare that they have no conflicts of interests.
