Application of proteomic profiling based on 2D-DIGE for classification of compounds according to the mechanism of action.
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.
Chemical Library Validation Team, Chemical Biology Core Facility, Chemical Biology Department, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Makoto
M
Muroi
Sayaka
S
Kazami
Kazue
K
Noda
Hisae
H
Kondo
Hiroshi
H
Takayama
Makoto
M
Kawatani
Takeo
T
Usui
Hiroyuki
H
Osada
D000970:Antineoplastic Agents / Q000145:classification* / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D016000:Cluster Analysis; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020543:Proteome / Q000032:analysis*; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D018942:Macrolides; D047428:Protein Kinase Inhibitors; D020543:Proteome; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II; C035359:monorden; C001277:geldanamycin