Dual role of NF-kappaB in apoptosis of THP-1 cells during treatment with etoposide and lipopolysaccharide

Leuk Res. 2004 Jan;28(1):63-9. doi: 10.1016/s0145-2126(03)00127-9.

Abstract

One of the mechanisms repressing apoptosis in tumor cells can involve the expression of anti-apoptotic NF-kappaB target genes. In this study, we demonstrated that a potent NF-kappaB inhibitor, Nalpha-tosyl-L-lysinyl chloromethyl ketone (TLCK), inhibits apoptosis of THP-1 cells triggered by etoposide (VP16), and actinomycin D (ACT D) or cycloheximide inhibits apoptosis. However, persistent activation of NF-kappaB by lipopolysaccharide (LPS) led to the survival of leukemic cells against VP16-induced apoptosis. Thus, the molecular events (Bax/X-chromosome-linked IAP (XIAP)) occurring downstream of NF-kappaB activation during VP16 and/or LPS stimulation may become important to understand the multiple effects of NF-kappaB.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis*
  • Caspase Inhibitors
  • Caspases / metabolism
  • Cycloheximide / pharmacology
  • Dactinomycin / pharmacology
  • Drug Therapy, Combination
  • Enzyme Inhibitors / pharmacology
  • Etoposide / pharmacology*
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Leukemia / metabolism
  • Leukemia / pathology*
  • Lipopolysaccharides / pharmacology*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Protein Synthesis Inhibitors / pharmacology
  • Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Tosyllysine Chloromethyl Ketone / pharmacology
  • Tumor Cells, Cultured
  • X-Linked Inhibitor of Apoptosis Protein
  • bcl-2-Associated X Protein

Substances

  • Antineoplastic Agents, Phytogenic
  • BAX protein, human
  • Caspase Inhibitors
  • Enzyme Inhibitors
  • Inhibitor of Apoptosis Proteins
  • Lipopolysaccharides
  • NF-kappa B
  • Protein Synthesis Inhibitors
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • bcl-2-Associated X Protein
  • Dactinomycin
  • Tosyllysine Chloromethyl Ketone
  • Etoposide
  • Cycloheximide
  • Caspases