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
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents, Phytogenic / pharmacology
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Apoptosis*
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Caspase Inhibitors
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Caspases / metabolism
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Cycloheximide / pharmacology
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Dactinomycin / pharmacology
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Drug Therapy, Combination
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Enzyme Inhibitors / pharmacology
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Etoposide / pharmacology*
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Humans
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Inhibitor of Apoptosis Proteins
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Leukemia / metabolism
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Leukemia / pathology*
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Lipopolysaccharides / pharmacology*
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism*
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Protein Synthesis Inhibitors / pharmacology
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Proteins / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Tosyllysine Chloromethyl Ketone / pharmacology
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Tumor Cells, Cultured
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X-Linked Inhibitor of Apoptosis Protein
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bcl-2-Associated X Protein
Substances
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Antineoplastic Agents, Phytogenic
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BAX protein, human
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Caspase Inhibitors
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Enzyme Inhibitors
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Inhibitor of Apoptosis Proteins
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Lipopolysaccharides
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NF-kappa B
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Protein Synthesis Inhibitors
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Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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X-Linked Inhibitor of Apoptosis Protein
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XIAP protein, human
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bcl-2-Associated X Protein
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Dactinomycin
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Tosyllysine Chloromethyl Ketone
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Etoposide
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Cycloheximide
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Caspases