TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB.
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.
Wang
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Curriculum in Genetics and Molecular Biology and Department of Endodontics, School of Dentistry, University of North Carolina, Chapel Hill, NC 27599-7295, USA.
Mayo
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MW
Baldwin
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D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002467:Cell Nucleus / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins; D007375:Interleukin-1 / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011839:Radiation, Ionizing; D019311:Staurosporine / Q000494:pharmacology; D051996:Transcription Factor RelA; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007375:Interleukin-1; D007976:Leupeptins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011500:Protein Synthesis Inhibitors; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D003513:Cycloheximide; D019311:Staurosporine; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D003630:Daunorubicin