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 arapid identification of their molecular mechanism of action. To make this step short wehave initiated the proteomic profiling of HeLa cells treated with the anticancer drugsrepresenting a wide spectrum of mechanisms of action, using 2D-DIGE. A uniqueproteome patterns were observed in HeLa cells treated with the HSP90 inhibitor,geldanamycin, and those were similar to the patterns induced by radicicol, anotherstructurally different HSP90 inhibitor. On the other hand, etoposide and ICRF-193, thecompounds claimed to be topoisomerase II inhibitors, showed different proteomicprofiles, which reflect their different biological activities as revealed by cell cycleanalysis. So far combined data from 19 compounds allowed their successful classificationby cluster analysis according to the mechanism of action