Abstract
Many cells are resistant to stimuli that can induce apoptosis, but the mechanisms involved are not fully understood. The activation of the transcription factor nuclear factor-kappa B (NF-kappaB) by tumor necrosis factor (TNF), ionizing radiation, or daunorubicin (a cancer chemotherapeutic compound), was found to protect from cell killing. Inhibition of NF-kappaB nuclear translocation enhanced apoptotic killing by these reagents but not by apoptotic stimuli that do not activate NF-kappaB. These results provide a mechanism of cellular resistance to killing by some apoptotic reagents, offer insight into a new role for NF-kappaB, and have potential for improvement of the efficacy of cancer therapies.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antibiotics, Antineoplastic / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Apoptosis* / drug effects
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Apoptosis* / radiation effects
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Cell Nucleus / metabolism
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Cycloheximide / pharmacology
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DNA-Binding Proteins / metabolism
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Daunorubicin / pharmacology*
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Humans
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I-kappa B Proteins*
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Interleukin-1 / pharmacology
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Leupeptins / pharmacology
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NF-KappaB Inhibitor alpha
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / metabolism
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NF-kappa B / physiology*
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Neoplasms / drug therapy
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Neoplasms / radiotherapy
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Protein Synthesis Inhibitors / pharmacology
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Radiation, Ionizing*
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Staurosporine / pharmacology
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Transcription Factor RelA
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / pharmacology*
Substances
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Antibiotics, Antineoplastic
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DNA-Binding Proteins
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I-kappa B Proteins
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Interleukin-1
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Leupeptins
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NF-kappa B
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NFKBIA protein, human
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Protein Synthesis Inhibitors
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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NF-KappaB Inhibitor alpha
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Cycloheximide
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Staurosporine
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benzyloxycarbonylleucyl-leucyl-leucine aldehyde
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Daunorubicin