Killing of lymphoblastic leukemia cells by nitric oxide and taxol: involvement of NF-kappa B activity

Nitric oxide (NO) and taxol are cytotoxic towards leukemia and tumor cells and interfere with the transcription factor NF-kappaB activity. NO and taxo l inhibited NF-kappaB activity and were cytotoxic to human and murine leuke mia cells, but at a different magnitude (30% cell killing and 80% inhibitio n of NF-kappaB). Sub-effective concentrations of SNAP and taxol synergized in killing L-1210 cells but either alone or in combination completely inhib ited 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 cytoskel eton. Our results show that NO, taxol and PDTC induced apoptosis and NF-kap paB inhibition in leukemic cells but their cytotoxicity either alone or in combination, does not seem to be dependent on the inhibition of NF-KB activ ity. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.