Syrosingopine sensitizes cancer cells to killing by metformin.
Syrosingopine sensitizes cancer cells to killing by metformin.
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DOI：
10.1126/sciadv.1601756
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发表时间：
2016-12
期刊：
影响因子：
13.6
通讯作者：
Hall MN
中科院分区：
文献类型：
--
作者：
Benjamin D;Colombi M;Hindupur SK;Betz C;Lane HA;El-Shemerly MY;Lu M;Quagliata L;Terracciano L;Moes S;Sharpe T;Wodnar-Filipowicz A;Moroni C;Hall MN
临床批准的非癌症药物二甲双胍和辛辛普林之间的合成致命性专门杀死癌细胞。我们报告了广泛使用的糖尿病药物二甲双胍的抗癌活性被辛辛普林强烈增强。这两种药物联合使用产生的合成杀伤力是协同的，并且对转化的细胞是特异的。这种作用与syrosingopine作为囊泡单胺转运体抑制剂的已知作用无关。在体外，Syrosingopine与糖酵解酶α-enolase结合，γ-enolase亚型的表达与药物组合的无反应性相关。Syrosingopine使癌细胞对二甲双胍及其更有效的衍生物苯福明的敏感度远远低于每种化合物的个体毒性阈值。因此，联合应用辛辛托品和辅药是一种很有前途的治疗策略，可用于癌症的临床治疗。
Synthetic lethality between the clinically approved noncancer drugs metformin and syrosingopine specifically kills cancer cells. We report that the anticancer activity of the widely used diabetic drug metformin is strongly potentiated by syrosingopine. Synthetic lethality elicited by combining the two drugs is synergistic and specific to transformed cells. This effect is unrelated to syrosingopine’s known role as an inhibitor of the vesicular monoamine transporters. Syrosingopine binds to the glycolytic enzyme α-enolase in vitro, and the expression of the γ-enolase isoform correlates with nonresponsiveness to the drug combination. Syrosingopine sensitized cancer cells to metformin and its more potent derivative phenformin far below the individual toxic threshold of each compound. Thus, combining syrosingopine and codrugs is a promising therapeutic strategy for clinical application for the treatment of cancer.
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影响因子：
--
作者：
Chae YK;Arya A;Malecek MK;Shin DS;Carneiro B;Chandra S;Kaplan J;Kalyan A;Altman JK;Platanias L;Giles F
通讯作者：
Giles F
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通讯作者：
Semenchenko, AV
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作者：
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通讯作者：
Kos, Janko