Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005, 149(2):413-417 | DOI: 10.5507/bp.2005.071

INVOLVEMENT OF GLUTATHIONE IN THE CYTOTOXICITY OF 9-ISOTHIOCYANATOACRIDINE

Helena Paulíková^a, Mária Bajdichová^a, Andrea Šovčíková^a, Danica Sabolová^b

^a Department of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak Technical University, Bratislava

^b Department of Biochemistry, Faculty of Science, P. J. Šafárik University, Košice

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, IC₅₀=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.

Keywords: Isothiocyanate, Thiol, Apoptosis, K562 cells

Received: June 10, 2005; Accepted: September 25, 2005; Published: December 1, 2005  Show citation