Application of Proteomic Profiling Based on 2D-DIGE for Classification of Compounds According to the Mechanism of Action

被引:66
作者
Muroi, Makoto [1 ]
Kazami, Sayaka [1 ,2 ]
Noda, Kazue [1 ]
Kondo, Hisae [1 ]
Takayama, Hiroshi [1 ,2 ]
Kawatani, Makoto [1 ]
Usui, Takeo [3 ]
Osada, Hiroyuki [1 ,2 ]
机构
[1] RIKEN Adv Sci Inst, Dept Biol Chem, Chem Biol Core Facil, Chem Lib Validat Team, Wako, Saitama 3510198, Japan
[2] Saitama Univ, Grad Sch Sci & Engn, Saitama 3388570, Japan
[3] Univ Tsukuba, Grad Sch Life & Environm Sci, Tsukuba, Ibaraki 3058572, Japan
来源
CHEMISTRY & BIOLOGY | 2010年 / 17卷 / 05期
关键词
DNA TOPOISOMERASE-II; TUBULIN POLYMERIZATION; ANTITUMOR-ACTIVITY; SMALL MOLECULES; INHIBITORS; TARGET; IDENTIFICATION; ANTIBIOTICS; EXPRESSION; PHALLOIDIN;
D O I
10.1016/j.chembiol.2010.03.016
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 He La 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 He La 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.
引用
收藏
页码:460 / 470
页数:11
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