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

Abstract

Nitric oxide (NO) and taxol are cytotoxic towards leukemia and tumor cells and interfere with the transcription factor NF-κB activity. NO and taxol inhibited NF-κB activity and were cytotoxic to human and murine leukemia cells, but at a different magnitude (30% cell killing and 80% inhibition of NF-κB). Sub-effective concentrations of SNAP and taxol synergized in killing L-1210 cells but either alone or in combination completely inhibited NF-κB. Pyrrolidine dithiocarbamate (PDTC) was cytotoxic on its own and inhibited NF-κB activity. It potentiated NO and taxol killing but again there was no direct relationship between inhibition of NF-κB 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-κB 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.