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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2008-11-25
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pubmed:abstractText |
Development of chemoresistance in androgen-refractory prostate cancer cells is partly due to constitutive activation of Rel/NF-kappaB transcription factors that regulate several cell survival and anti-apoptotic genes. In this study we examined whether betulinic acid (BetA), a pentacyclic triterpene from the bark of white birch, is effective in inhibiting NF-kappaB expression in androgen-refractory human prostate cancer cells exhibiting high constitutive NF-kappaB expression. Treatment of PC-3 cells with BetA inhibited DNA binding and reduced nuclear levels of the NF-kappaB/p65. BetA-mediated NF-kappaB inhibition involved decreased IKK activity and phosphorylation of IkappaBalpha at serine 32/36 followed by its degradation. Reporter assays revealed that NF-kappaB inhibition by BetA is transcriptionally active. These effects were found to correlate with a shift in Bax/Bcl-2 ratio and cleavage of poly(ADP)ribose polymerase more towards apoptosis. BetA also inhibited TNFalpha-induced activation of NF-kappaB via the IkappaBalpha pathway, thereby sensitizing the cells to TNFalpha-induced apoptosis. Our studies demonstrate that BetA effectively inhibits constitutive NF-kappaB activation and supports the rationale for targeting NF-kappaB through combination protocols with BetA in androgen-refractory prostate cancer.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18444250-10029068,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18444250-10602468,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18444250-10771474,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18444250-17363604,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18444250-18056430,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18444250-7489361,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18444250-8170948,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18444250-9280312,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18444250-9354463,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18444250-9525100,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18444250-9572490
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1098-2744
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
47
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
964-73
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pubmed:dateRevised |
2010-12-3
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pubmed:meshHeading |
pubmed-meshheading:18444250-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:18444250-Apoptosis,
pubmed-meshheading:18444250-Cell Line, Tumor,
pubmed-meshheading:18444250-Cell Survival,
pubmed-meshheading:18444250-Dose-Response Relationship, Drug,
pubmed-meshheading:18444250-Formazans,
pubmed-meshheading:18444250-Genes, Reporter,
pubmed-meshheading:18444250-Humans,
pubmed-meshheading:18444250-Luciferases,
pubmed-meshheading:18444250-Male,
pubmed-meshheading:18444250-NF-kappa B,
pubmed-meshheading:18444250-Prostatic Neoplasms,
pubmed-meshheading:18444250-Tetrazolium Salts,
pubmed-meshheading:18444250-Time Factors,
pubmed-meshheading:18444250-Transfection,
pubmed-meshheading:18444250-Triterpenes,
pubmed-meshheading:18444250-Tumor Necrosis Factor-alpha
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pubmed:year |
2008
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pubmed:articleTitle |
Betulinic acid suppresses constitutive and TNFalpha-induced NF-kappaB activation and induces apoptosis in human prostate carcinoma PC-3 cells.
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