Involvement of glutathione in the cytotoxicity of 9-isothiocyanatoacridine.
Isothiocyanates (ITCs) are phytochemicals with promising cancer-preventive potential. To elucidate the mechanism of cytotoxicity of ITCs, their accumulation by cells and the role of intracellular glutathione, fluorescent 9-isothiocyanatoacridine (AcITC) was synthesized. The kinetic parameters for the reactions of AcITC with thiols were estimated and the influence of AcITC on human chronic myeloid leukemia cell line (K562) in regard to intracellular glutathione was studied. Cytotoxicity was evaluated by MTT assay, IC(50)=29.2 +/- 2.5 microM (48 h incubation). This acridine derivative was able to induce apoptosis of cells (morphological changes of cells and DNA fragmentation were observed) at least within certain dose that only decreased the level of intracellular glutathione, excessive doses (completely depleted intracellular pool of glutathione) induced necrosis rather than apoptosis. Our results indicated that apoptosis of leukemia cells induced by ITC is possible only if intracellular glutathione is not entirely depleted.
Paulíková
Helena
H
Department of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak Technical University, Bratislava. helena.paulikova@stuba.sk
Bajdichová
Mária
M
Sovcíková
Andrea
A
Sabolová
Danica
D
D000166:Acridines / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D007939:Leukemia L1210; D051379:Mice; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000166:Acridines; C005921:isothiocyanatoacridine; D005978:Glutathione