Differential sensitivity of ovarian carcinoma cell lines to apoptosis induced by the IMPDH inhibitor benzamide riboside

The differential sensitivity of examined human ovarian cal carcinoma cell l ines (CH1, A-2780 and SKOV-3) to the IMPDH inhibitor, benzamide riboside (B R), was demonstrated with the aid of MTT assay. Present data show that all three examined ovarian carcinoma cell lines were sensitive to the cytotoxic effects of BR in the order of sensitivity CH1, SKOV-3, A-2780, (IC50 = 2.8 , 4.0 and 7.4 muM, respectively). Although the IC50 of SKOV-3 cells was sim ilar to that previously determined by others. more than 20% of SKOV-3 cells remained viable in a plateau up to 40 muM BR concentration. This relative resistance of SKOV-3 cells to BR corresponded to the absence of BR-induced apoptosis in SKOV-3 cells, which together with clearly demonstrated sensiti vity of CH1 cells to BR-induced apoptosis, established by flow cytometry (p resence of nuclei with sub-G(0) DNA content, Annexin V binding) and western blotting (poly-ADP-ribosyl-polymerase (PARP) cleavage), further stressed t he role of drug-induced apoptosis in the overall drug-induced cytotoxicity.