An B, Jin J R, Lin P, Dou Q P
Department of Pharmacology, University of Pittsburgh School of Medicine, PA 15213-2582, USA.
FEBS Lett. 1996 Dec 9;399(1-2):158-62. doi: 10.1016/s0014-5793(96)01311-7.
We previously found that retinoblastoma (RB) is cleaved at the initiation of apoptotic execution. Here we report that when an HL-60 cell line resistant to cytosine arabinoside (Ara-C) was exposed to this anticancer drug, neither RB cleavage nor apoptosis was detected. Consistent with that, processing of interleukin 1beta-converting enzyme (ICE) and CPP32 (an ICE-like protease) was also prevented in these cells. In contrast, treatment of the HL-60-Ara-C-resistant cells with etoposide induced all of these apoptotic events. Furthermore, the etoposide-induced RB cleavage was inhibited by a specific tetrapeptide ICE-like inhibitor. Our results demonstrate that activation of the RB cleavage enzyme, an ICE-like protease, is required for overcoming drug resistance.
我们先前发现，视网膜母细胞瘤（RB）在凋亡执行开始时会被切割。在此我们报告，当对阿糖胞苷（Ara-C）耐药的HL-60细胞系暴露于这种抗癌药物时，未检测到RB切割和凋亡。与此一致的是，这些细胞中白细胞介素1β转换酶（ICE）和CPP32（一种ICE样蛋白酶）的加工也受到抑制。相比之下，用依托泊苷处理HL-60-Ara-C耐药细胞会诱导所有这些凋亡事件。此外，依托泊苷诱导的RB切割被一种特异性四肽ICE样抑制剂所抑制。我们的结果表明，克服耐药性需要激活RB切割酶，一种ICE样蛋白酶。
