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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
36
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pubmed:dateCreated |
2000-10-2
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pubmed:abstractText |
The transcription factor nuclear factor-kappaB (NF-kappaB) regulates genes important for tumor invasion, metastasis and chemoresistance. Normally, NF-kappaB remains sequestered in an inactive state by cytoplasmic inhibitor-of-kappaB (IkappaB) proteins. NF-kappaB translocates to nucleus and activates gene expression upon exposure of cells to growth factors and cytokines. We and others have shown previously that NF-kappaB is constitutively active in a subset of breast cancers. In this study, we show that constitutive activation of NF-kappaB leads to overexpression of the anti-apoptotic genes c-inhibitor of apoptosis 2 (c-IAP2) and manganese superoxide dismutase (Mn-SOD) in breast cancer cells. Furthermore, expression of the anti-apoptotic tumor necrosis factor receptor associated factor 1 (TRAF1) and defender-against cell death (DAD-1) is regulated by NF-kappaB in certain breast cancer cells. We also demonstrate that NF-kappaB-inducible genes protect cancer cells against paclitaxel as MDA-MB-231 breast cancer cells modified to overexpress IkappaBalpha required lower concentrations of paclitaxel to arrest at the G2/M phase of the cell cycle and undergo apoptosis when compared to parental cells. The effect of NF-kappaB on paclitaxel-sensitivity appears to be specific to cancer cells because normal fibroblasts derived from embryos lacking p65 subunit of NF-kappaB and wild type littermate embryos were insensitive to paclitaxel-induced G2/M cell cycle arrest. Parthenolide, an active ingredient of herbal remedies such as feverfew (tanacetum parthenium), mimicked the effects of IkappaBalpha by inhibiting NF-kappaB DNA binding activity and Mn-SOD expression, and increasing paclitaxel-induced apoptosis of breast cancer cells. These results suggest that active ingredients of herbs with anti-inflammatory properties may be useful in increasing the sensitivity of cancers with constitutively active NF-kappaB to chemotherapeutic drugs. Oncogene (2000) 19, 4159 - 4169
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Caenorhabditis elegans Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dad-1 protein, C elegans,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Paclitaxel,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sesquiterpenes,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/TNF Receptor-Associated Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/parthenolide
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0950-9232
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pubmed:author |
pubmed-author:Bhat-NakshatriPP,
pubmed-author:BoswellS HSH,
pubmed-author:GelfanovVV,
pubmed-author:GouletR JRJJr,
pubmed-author:NakshatriHH,
pubmed-author:NewtonT RTR,
pubmed-author:NozakiSS,
pubmed-author:PatelN MNM,
pubmed-author:RiceSS,
pubmed-author:ShortleN HNH,
pubmed-author:SledgeG WGWJr
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4159-69
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10962577-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:10962577-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:10962577-Apoptosis,
pubmed-meshheading:10962577-Apoptosis Regulatory Proteins,
pubmed-meshheading:10962577-Blotting, Northern,
pubmed-meshheading:10962577-Blotting, Western,
pubmed-meshheading:10962577-Breast Neoplasms,
pubmed-meshheading:10962577-Caenorhabditis elegans Proteins,
pubmed-meshheading:10962577-DNA,
pubmed-meshheading:10962577-DNA-Binding Proteins,
pubmed-meshheading:10962577-Drug Synergism,
pubmed-meshheading:10962577-Female,
pubmed-meshheading:10962577-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:10962577-Humans,
pubmed-meshheading:10962577-I-kappa B Proteins,
pubmed-meshheading:10962577-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:10962577-NF-kappa B,
pubmed-meshheading:10962577-Paclitaxel,
pubmed-meshheading:10962577-Plants, Medicinal,
pubmed-meshheading:10962577-Protein Binding,
pubmed-meshheading:10962577-Proteins,
pubmed-meshheading:10962577-Repressor Proteins,
pubmed-meshheading:10962577-Sesquiterpenes,
pubmed-meshheading:10962577-Superoxide Dismutase,
pubmed-meshheading:10962577-TNF Receptor-Associated Factor 1,
pubmed-meshheading:10962577-Tumor Cells, Cultured
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pubmed:year |
2000
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pubmed:articleTitle |
Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor and parthenolide.
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pubmed:affiliation |
Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, IN 46202, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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