Comparative study of antiproliferative effects of chlorpromazine, 7,8-dioxochlorpromazine, amantadine-N-mustard, rutin-N-mustard and alpha, beta and gamma interferon on K-562 cells in vitro.
The effects of rutin-N-mustard, amantadine-N-mustard, chlorpromazine and human interferon types alpha, beta and gamma (IFN-alpha, -beta and -gamma) were studied on the DNA, RNA and protein synthesis of K-562 cells. Monocyte-mediated cytotoxicity and immune spleen cell activity were examined in the presence of the same compounds (except for IFN-beta). The natural killer (NK) cell activity was tested in the presence of the two chlorpromazine compounds and the two N-mustard derivatives. Only 7,8-dioxochlorpromazine exerted an inhibitory effect on DNA synthesis. The protein synthesis of the cells was inhibited in the presence of IFN-alpha, -beta and -gamma. 7,8-Dioxochlorpromazine exerted some inhibition on both NK and immune spleen cell activity, while monocyte-mediated cytolysis was not altered. IFN-alpha, -beta and -gamma activated the cytolytic activity of monocytes and the NK activity in control experiments. Chlorpromazine, rutin-N-mustard and amantadine-N-mustard were ineffective in both tests in vitro. Rutin-N-mustard, 7,8-dioxochlorpromazine and the interferons may be assumed to have quite different antiproliferative mechanisms of actions.
D000547:Amantadine / Q000031:analogs & derivatives* / Q000633:toxicity; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002746:Chlorpromazine / Q000031:analogs & derivatives* / Q000633:toxicity*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000633:toxicity*; D007371:Interferon-gamma / Q000633:toxicity*; D007951:Leukemia, Myeloid; D009000:Monocytes / Q000276:immunology; D009588:Nitrogen Mustard Compounds / Q000633:toxicity*; D014176:Protein Biosynthesis / Q000187:drug effects; D012431:Rutin / Q000031:analogs & derivatives* / Q000633:toxicity; D014158:Transcription, Genetic / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D007370:Interferon Type I; D009588:Nitrogen Mustard Compounds; C026713:7,8-dioxochlorpromazine; C049207:amantadine-N-mustard; D012431:Rutin; D007371:Interferon-gamma; C036960:rutin-N-mustard; D000547:Amantadine; D002746:Chlorpromazine