Weltin D, Marchal J, Dufour P, Potworowski E, Oth D, Bischoff P
Institut d'Hématologie et d'Immunologie, Strasbourg, France.
Oncol Res. 1994;6(9):399-403.
By catalyzing posttranslational modifications of nuclear proteins, poly(ADP-ribose) polymerase (PARP) controls their functions and therefore constitutes an enzyme of crucial importance in tumor development. In this study, we have investigated the action of 6(5H)-phenanthridinone, an isoquinoline derivative and one of the most potent PARP inhibitors described so far, on RDM4 murine lymphoma cells in culture. We also examined whether this compound could act synergistically with an antineoplastic drug in tumor-cell destruction. Our results demonstrate that a marked inhibition of PARP activity can be obtained in whole cells after a short incubation, and that this compound, when associated with an alkylating agent, dichloro-2,2' N-methyldiethylamine (chloromethine), leads to a marked drop in the RDM4 proliferation, indicative of a synergy between the two compounds.
通过催化核蛋白的翻译后修饰，聚（ADP - 核糖）聚合酶（PARP）控制其功能，因此是肿瘤发展中至关重要的一种酶。在本研究中，我们研究了6（5H）-菲啶酮（一种异喹啉衍生物，也是迄今为止描述的最有效的PARP抑制剂之一）对培养的RDM4小鼠淋巴瘤细胞的作用。我们还研究了该化合物是否能与一种抗肿瘤药物协同作用以破坏肿瘤细胞。我们的结果表明，短时间孵育后在全细胞中可获得对PARP活性的显著抑制，并且该化合物与烷基化剂二氯 - 2,2' - N - 甲基二乙胺（氯芥）联合使用时，会导致RDM4细胞增殖显著下降，表明这两种化合物之间存在协同作用。
