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.
- MeSH
- akridiny toxicita MeSH
- apoptóza účinky léků MeSH
- buňky K562 MeSH
- fragmentace DNA účinky léků MeSH
- glutathion metabolismus MeSH
- leukemie L1210 MeSH
- lidé MeSH
- myši MeSH
- nádorové buňky kultivované účinky léků MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- biopolymery chemie metabolismus MeSH
- cytochromy c chemie metabolismus MeSH
- membránové lipidy chemie MeSH
- membránové proteiny chemie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- techniky in vitro MeSH
