Targeting on poly(ADP-ribose) polymerase activity with DNA-damaging hybrid lactam-steroid alkylators in wild-type and BRCA1-mutated ovarian cancer cells,Chemical Biology & Drug Design

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Targeting on poly(ADP-ribose) polymerase activity with DNA-damaging hybrid lactam-steroid alkylators in wild-type and BRCA1-mutated ovarian cancer cells
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2017-05-26 05:10:32 , DOI: 10.1111/cbdd.13006
Dimitrios T. Trafalis ₁ , Aikaterini Polonifi ₁ , Panayiotis Dalezis ₁ , Nikolaos Nikoleousakos ₁ , Sotirios Katsamakas ₂ , Vasiliki Sarli ₃

Affiliation

Conjugated lactam-steroid alkylators (LSA) have been shown to exhibit superior activity at controlling cancer models and overlap drug resistance to conventional chemjournalapy. LSA produce anticancer activity through dual action by combining the direct induction of cellular DNA damage with the inhibition of PARP activity and consecutive DNA repair activity, as well as modulating PARP1/2 mRNA transcription. BRCA1-mutated UWB1.289 ovarian cancer cells with defective PARP-oriented repair mechanism show significantly higher sensitivity to these agents.

中文翻译：

针对野生型和BRCA1突变的卵巢癌细胞中具有DNA破坏性的混合内酰胺类固醇烷基化剂的聚（ADP-核糖）聚合酶活性。

共轭内酰胺-类固醇烷基化剂（LSA）已显示出在控制癌症模型中具有优越的活性，并且对常规的化学假性尿嘧啶具有重叠的耐药性。LSA通过将细胞DNA损伤的直接诱导与对PARP活性的抑制和连续的DNA修复活性相结合，并调节PARP1 / 2 mRNA的转录，通过双重作用产生抗癌活性。具有缺陷的PARP导向修复机制的BRCA1突变的UWB1.289卵巢癌细胞对这些药物的敏感性显着提高。

更新日期：2017-11-01

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