Selective inhibition of MCF-7(piGST) breast tumors using glutathione transferase-derived 2-methylene-cycloalkenones.
Selective inhibition of MCF-7(piGST) breast tumors using glutathione transferase-derived 2-methylene-cycloalkenones.
复制标题
使用谷胱甘肽转移酶衍生的 2-亚甲基环烯酮选择性抑制 MCF-7(piGST) 乳腺肿瘤。
DOI：
10.1021/jm058245f
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Creighton,DonaldJ
中科院分区：
文献类型：
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作者：
Joseph,Erin;Ganem,Bruce;Eiseman,JulieL;Creighton,DonaldJ
人谷胱甘肽（GSH）转移酶（hGSTP 1 -1）催化抗肿瘤的2-巴豆酰氧基甲基-2-环烯酮（COMC）转化为高反应性的环外烯酮烷化剂。体外功效研究显示，COMC的细胞毒性与MCF-7 piGST与MCF-7 wt乳腺肿瘤中GSTP 1 -1的表达水平直接相关，表明环外烯酮是实际的细胞毒性物质。COMCs是一类潜在的重要的新型前药，其可以特异性靶向过表达hGSTP 1 -1的多药耐药肿瘤。
Human glutathione (GSH) transferase (hGSTP1-1) catalyzes the conversion of antitumor 2-crotonyloxymethyl-2-cycloalkenones (COMCs) to highly reactive exocyclic enone alkylating agents. In vitro efficacy studies show that the cytotoxicities of the COMCs directly correlate with the level of expression of GSTP1-1 in MCF-7piGSTversus MCF-7wt breast tumors, indicating that the exocyclic enones are the actual cytotoxic species. The COMCs are a potentially important new class of prodrugs, which can specifically target multi-drug-resistant tumors overexpressing hGSTP1-1.