PT Journal
AU Paulikova, H
   Bajdichova, M
   Sovcikova, A
   Sabolova, D
TI INVOLVEMENT OF GLUTATHIONE IN THE CYTOTOXICITY OF 9-ISOTHIOCYANATOACRIDINE
SO Biomedical papers
PY 2005
BP 413
EP 417
VL 149
IS 2
DI 10.5507/bp.2005.071
DE Isothiocyanate/Thiol/Apoptosis/K562 cells
AB 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<sub>50</sub>=29.2 ± 2.5 μM (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.
ER