Killing of lymphoblastic leukemia cells by nitric oxide and taxol: involvement of NF-kappaB activity.
Nitric oxide (NO) and taxol are cytotoxic towards leukemia and tumor cells and interfere with the transcription factor NF-kappaB activity. NO and taxol inhibited NF-kappaB activity and were cytotoxic to human and murine leukemia cells, but at a different magnitude (30% cell killing and 80% inhibition of NF-kappaB). Sub-effective concentrations of SNAP and taxol synergized in killing L-1210 cells but either alone or in combination completely inhibited NF-kappaB. Pyrrolidine dithiocarbamate (PDTC) was cytotoxic on its own and inhibited NF-kappaB activity. It potentiated NO and taxol killing but again there was no direct relationship between inhibition of NF-kappaB and cell killing. Neither NO nor taxol cytotoxicity was related to the cytoskeleton. Our results show that NO, taxol and PDTC induced apoptosis and NF-kappaB inhibition in leukemic cells but their cytotoxicity either alone or in combination, does not seem to be dependent on the inhibition of NF-KB activity.
Santos-Silva
M C
MC
Department of Clinical Analysis, Center of Health Sciences, Universidade Federal de Santa Catarina, Florianópolis SC, 88015-420, Brazil.
Sampaio de Freitas
M
M
Assreuy
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D007939:Leukemia L1210 / Q000378:metabolism / Q000473:pathology*; D007945:Leukemia, Lymphoid / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016328:NF-kappa B; D020030:Nitric Oxide Donors; D011500:Protein Synthesis Inhibitors; D011759:Pyrrolidines; C110881:S-nitro-N-acetylpenicillamine; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D010396:Penicillamine; D017239:Paclitaxel