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

Cancer Lett. 2001 Nov 8;173(1):53-61. doi: 10.1016/s0304-3835(01)00664-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Survival / drug effects
  • Cytoskeleton / drug effects
  • Drug Synergism
  • Humans
  • Leukemia L1210 / metabolism
  • Leukemia L1210 / pathology*
  • Leukemia, Lymphoid / metabolism
  • Leukemia, Lymphoid / pathology*
  • Mice
  • Molsidomine / analogs & derivatives*
  • Molsidomine / pharmacology
  • NF-kappa B / antagonists & inhibitors*
  • Nitric Oxide / physiology*
  • Nitric Oxide Donors / pharmacology
  • Paclitaxel / pharmacology*
  • Penicillamine / analogs & derivatives*
  • Penicillamine / pharmacology
  • Protein Synthesis Inhibitors / pharmacology
  • Pyrrolidines / pharmacology
  • Thiocarbamates / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • NF-kappa B
  • Nitric Oxide Donors
  • Protein Synthesis Inhibitors
  • Pyrrolidines
  • S-nitro-N-acetylpenicillamine
  • Thiocarbamates
  • pyrrolidine dithiocarbamic acid
  • Nitric Oxide
  • linsidomine
  • Molsidomine
  • Penicillamine
  • Paclitaxel