Comparison of inhibition of murine leukaemia cell growth by 9-isothiocyanatoacridine and its cytosine adduct: involvement of thiols.
Cytotoxicity of two fluorescent acridine derivatives - 9-isothiocyanatoacridine (AcITC) and N-(9-acridinylthiocarbamoyl) cytosine (AcTCC) - a novel acridine compound, were investigated. Both substances have cytotoxic activity against the L1210 cellular line, IC50 values were in the micromolar range. Despite the high reactivity of AcITC towards thiols, its effects on leukemia cells were similar to naturally occurring isothiocyanates. AcITC changed the intracellular level of glutathione (GSH), and induced apoptosis. Arrest of cell cycle (G2/M-phase) was also observed. AcITC primarily reacted with -SH groups on cellular surface, and the study of the interaction of the isotiocyanate with human erythrocyte ghosts confirmed that the plasma membrane was the first place where AcITC bound. AcTCC does not react with cellular thiols; images obtained with fluorescent microscopy confirmed interaction of AcTCC with chromatine. Although AcTCC induced cellular arrest in the G2/M phase, apoptosis was not confirmed.
Bajdichova
M
M
Department of Biochemistry and Microbiology, Slovak University of Technology, Radlinského 9, 81237, Bratislava, Slovakia.
Paulikova
H
H
Jakubikova
J
J
Sabolova
D
D
D000166:Acridines / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003596:Cytosine / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry / Q000633:toxicity*; D004910:Erythrocyte Membrane / Q000187:drug effects; D005434:Flow Cytometry; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D000166:Acridines; D018736:DNA Adducts; D013438:Sulfhydryl Compounds; C005921:isothiocyanatoacridine; D003596:Cytosine; D005978:Glutathione