Differential sensitivity of ovarian carcinoma cell lines to apoptosis induced by the IMPDH inhibitor benzamide riboside.
The differential sensitivity of examined human ovarian carcinoma cell lines (CH1, A-2780 and SKOV-3) to the IMPDH inhibitor, benzamide riboside (BR), 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 microM, respectively). Although the IC50 of SKOV-3 cells was similar to that previously determined by others, more than 20% of SKOV-3 cells remained viable in a plateau up to 40 microM BR concentration. This relative resistance of SKOV-3 cells to BR corresponded to the absence ofBR-induced apoptosis in SKOV-3 cells, which together with clearly demonstrated sensitivity of CH1 cells to BR-induced apoptosis, established by flow cytometry (presence of nuclei with sub-G0 DNA content, Annexin V binding) and western blotting (poly-ADP-ribosyl-polymerase (PARP) cleavage), further stressed the role of drug-induced apoptosis in the over-all drug-induced cytotoxicity.
Hunáková
L
L
Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic. exonhun@savba.sk
Bies
J
J
Sedlák
J
J
Duraj
J
J
Jakubíková
J
J
Takácsová
X
X
Novotný
L
L
Chorváth
B
B
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005260:Female; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D009705:Nucleosides / Q000633:toxicity*; D010051:Ovarian Neoplasms / Q000473:pathology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D009705:Nucleosides; C076145:3-(1-deoxyribofuranosyl)benzamide; D007168:IMP Dehydrogenase; D011065:Poly(ADP-ribose) Polymerases