Muroi Makoto, Kazami Sayaka, Noda Kazue, Kondo Hisae, Takayama Hiroshi, Kawatani Makoto, Usui Takeo, Osada Hiroyuki
Chemical Library Validation Team, Chemical Biology Core Facility, Chemical Biology Department, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Chem Biol. 2010 May 28;17(5):460-70. doi: 10.1016/j.chembiol.2010.03.016.
The development of new anticancer agents derived from natural resources requires a rapid identification of their molecular mechanism of action. To make this step short, we have initiated the proteomic profiling of HeLa cells treated with anticancer drugs representing a wide spectrum of mechanisms of action using two-dimensional difference gel electrophoresis (2D-DIGE). Unique proteome patterns were observed in HeLa cells treated with the HSP90 inhibitor geldanamycin, and were similar to the patterns induced by radicicol, a structurally different HSP90 inhibitor. On the other hand, etoposide and ICRF-193, compounds claimed to be topoisomerase II inhibitors, showed different proteomic profiles, which reflect their different biological activities as revealed by cell-cycle analysis. Thus far, combined data from 19 compounds have allowed their successful classification by cluster analysis according to the mechanism of action.
开发源自自然资源的新型抗癌药物需要快速确定其分子作用机制。为了缩短这一步骤，我们利用二维差异凝胶电泳（2D-DIGE），对用代表广泛作用机制的抗癌药物处理的HeLa细胞进行了蛋白质组分析。在用热休克蛋白90（HSP90）抑制剂格尔德霉素处理的HeLa细胞中观察到了独特的蛋白质组模式，并且与由结构不同的HSP90抑制剂雷迪西醇诱导的模式相似。另一方面，依托泊苷和ICRF-193这两种声称是拓扑异构酶II抑制剂的化合物，显示出不同的蛋白质组图谱，这反映了通过细胞周期分析揭示的它们不同的生物学活性。到目前为止，来自19种化合物的综合数据已允许根据作用机制通过聚类分析对它们成功分类。
