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Toxins 2017, 9(7), 208;

Prenylflavonoid Isoxanthohumol Sensitizes MCF-7/ADR Cells to Doxorubicin Cytotoxicity via Acting as a Substrate of ABCB1

1,2,* , 1
Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
Southern Research Institute, 2000 9th Avenue South, Birmingham, AL 35205, USA
Key Laboratory of Marine Bioactive Substance, The First Institute of Oceanography, State Oceanic Administration, Qingdao 266061, China
Authors to whom correspondence should be addressed.
Academic Editor: Carmela Fimognari
Received: 30 April 2017 / Revised: 8 June 2017 / Accepted: 26 June 2017 / Published: 30 June 2017
(This article belongs to the Section Plant Toxins)
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Isoxanthohumol is a unique prenylflavonoid with the highest content in beer. Isoxanthohumol has multiple bioactivities and has recently received considerable attention in the scientific community. Nonetheless; its effect on drug resistant cancer cells has rarely been studied. In this paper; we investigated the synergistic effect of isoxanthohumol and doxorubicin on doxorubicin resistant MCF-7/ADR cells. Our results showed that isoxanthohumol sensitized the cytotoxic effect of doxorubicin on MCF-7/ADR cells via increased proliferation inhibition and apoptosis stimulation. Molecular mechanism studies further demonstrated that isoxanthohumol inhibited ABCB1-mediated doxorubicin efflux; stimulated the ATPase activity of ABCB1 (ATP-binding cassette sub-family B member 1); and acted as an ABCB1 substrate. Molecular docking results suggested that isoxanthohumol bound to the central transmembrane domain of ABCB1 and its binding site overlapped with the doxorubicin binding site. The present studies demonstrated that isoxanthohumol was a competitive ABCB1 inhibitor which reversed ABCB1-mediated doxorubicin resistance in MCF-7/ADR cells; and therefore could be further developed to help with overcoming ABCB1-mediated drug resistance. View Full-Text
Keywords: isoxanthohumol; doxorubicin resistance; synergism; ABCB1 isoxanthohumol; doxorubicin resistance; synergism; ABCB1

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Liu, M.; Zhang, W.; Zhang, W.; Zhou, X.; Li, M.; Miao, J. Prenylflavonoid Isoxanthohumol Sensitizes MCF-7/ADR Cells to Doxorubicin Cytotoxicity via Acting as a Substrate of ABCB1. Toxins 2017, 9, 208.

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