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.
Muroi
Makoto
M
Chemical Library Validation Team, Chemical Biology Core Facility, Chemical Biology Department, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Kazami
Sayaka
S
Noda
Kazue
K
Kondo
Hisae
H
Takayama
Hiroshi
H
Kawatani
Makoto
M
Usui
Takeo
T
Osada
Hiroyuki
H
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