Prenylflavonoid Isoxanthohumol Sensitizes MCF-7/ADR Cells to Doxorubicin Cytotoxicity via Acting as a Substrate of ABCB1.
Prenylflavonoid Isoxanthohumol Sensitizes MCF-7/ADR Cells to Doxorubicin Cytotoxicity via Acting as a Substrate of ABCB1.
复制标题
异黄酮异黄腐酚通过作为 ABCB1 的底物使 MCF-7/ADR 细胞对阿霉素细胞毒性敏感
DOI：
10.3390/toxins9070208
复制
发表时间：
2017-06-30
期刊：
影响因子：
4.2
通讯作者：
Miao J
中科院分区：
文献类型：
--
作者：
Liu M;Zhang W;Zhang W;Zhou X;Li M;Miao J
异黄腐酚是啤酒中含量最高的一种异戊烯类黄酮。异黄腐酚具有多种生物活性，最近在科学界受到了相当大的关注。尽管如此，它对耐药癌细胞的影响很少被研究。本文研究了异黄腐酚和阿霉素对阿霉素耐药MCF-7/ADR细胞的协同作用。我们的研究结果表明，异黄腐酚敏化阿霉素对MCF-7/ADR细胞的细胞毒性作用，通过增加增殖抑制和凋亡刺激。分子机制研究进一步表明，异黄腐酚抑制ABCB 1介导的阿霉素外排;刺激ABCB 1（ATP结合盒亚家族B成员1）的ATP酶活性;并作为ABCB 1底物。分子对接结果表明，异黄腐酚与ABCB 1的中央跨膜区结合，其结合位点与阿霉素的结合位点重叠。目前的研究表明，异黄腐酚是一种竞争性的ABCB 1抑制剂，可以逆转MCF-7/ADR细胞中ABCB 1介导的阿霉素耐药性;因此，可以进一步开发，以帮助克服ABCB 1介导的耐药性。
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.
登录
查看更多内容
DOI：
10.1016/j.bbagen.2012.12.005
发表时间：
2013-03-01
影响因子：
3
作者：
Kang, Youra;Park, Min-A;Kim, Jung-Ae
通讯作者：
Kim, Jung-Ae
影响因子：
5.2
作者：
Lohner, Katrin;Schnaebele, Kerstin;Wenzel, Uwe
通讯作者：
Wenzel, Uwe
影响因子：
3.4
作者：
Zolnierczyk, Anna Katarzyna;Maczka, Wanda Krystyna;Aniol, Miroslaw
通讯作者：
Aniol, Miroslaw
影响因子：
2.9
作者：
Venkatachalam, CM;Jiang, X;Waldman, M
通讯作者：
Waldman, M
配体进入，可延展结合和诱导螺旋蛋白的螺旋运动的快照。
DOI：
10.1107/s1399004715000978
发表时间：
2015-03
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Szewczyk P;Tao H;McGrath AP;Villaluz M;Rees SD;Lee SC;Doshi R;Urbatsch IL;Zhang Q;Chang G
通讯作者：
Chang G