Holl V, Coelho D, Weltin D, Hyun J W, Dufour P, Bischoff P
Laboratoire de Cancérologie Expérimentale et de Radiobiologie (LCER), Université Louis Pasteur, Faculté de Médecine, Strasbourg, France.
Anticancer Res. 2000 Sep-Oct;20(5A):3233-41.
Poly (ADP-ribose) polymerase (PARP) is involved in the cellular responses to genotoxic damage and its inhibition has been proposed as potentiating anticancer drug activity. Here, we evaluated the ability of the PARP inhibitor, 6(5H)-phenanthridinone, to modulate the antiproliferative activity of bleomycin, carmustin and doxorubicin in a murine (RDM4) and a human (U937) lymphoma cell lines. 6(5H)-phenanthridinone was shown to suppress PARP activity with the same potency in both cell lines. At 25 microM, this compound potentiated the activity of carmustin in RDM4 but not in U937 cells. In contrast, 6(5H)-phenanthridinone failed to affect the doxorubicin toxicity in murine lymphoma cells, whereas it prevented the cytotoxicity of this drug in the human cell line. Altogether, these findings indicated that 6(5H)-phenanthridinone modulates the cytotoxicity of anticancer agents differently according to the cell type and the drug. Therefore, this PARP inhibitor could be considered as the prototype of a new class of adjuncts in cancer chemotherapy.
聚（ADP - 核糖）聚合酶（PARP）参与细胞对基因毒性损伤的反应，其抑制作用被认为可增强抗癌药物的活性。在此，我们评估了PARP抑制剂6(5H)-菲啶酮调节博来霉素、卡莫司汀和阿霉素对小鼠（RDM4）和人（U937）淋巴瘤细胞系抗增殖活性的能力。结果显示，6(5H)-菲啶酮在两种细胞系中均以相同效力抑制PARP活性。在25微摩尔浓度时，该化合物增强了卡莫司汀对RDM4细胞的活性，但对U937细胞无此作用。相反，6(5H)-菲啶酮不影响阿霉素对小鼠淋巴瘤细胞的毒性，却能阻止该药物对人细胞系的细胞毒性。总之，这些发现表明，6(5H)-菲啶酮根据细胞类型和药物不同，对抗癌药物的细胞毒性调节作用也不同。因此，这种PARP抑制剂可被视为癌症化疗新型辅助药物的原型。
