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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2008-6-3
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pubmed:abstractText |
Patients with hormone-refractory prostate cancer (HRPC) have an estimated median survival of only 10 months because of acquired drug resistance, urging the need to develop therapies against the drug-resistant HRPC phenotype. Accumulating evidence suggests that overexpressing antiapoptotic Bcl-2 family proteins is at least partially responsible for the development of drug resistance among HRPC patients. Antagonizing the antiapoptotic Bcl-2 family proteins, therefore, is one potential approach to circumventing drug resistance in HRPC. WL-276 was developed as a small-molecule antagonist against antiapoptotic Bcl-2 family proteins, with binding potency comparable to (-)-gossypol. Overexpressing Bcl-2 or Bcl-X(L) failed to confer resistance to WL-276. WL-276 also effectively induced apoptosis in PC-3 cells. In addition, three PC-3 cell lines with acquired drug resistance against standard cancer chemotherapies were more sensitive to WL-276 than the parent PC-3 cell line. The increased cytotoxicity toward drug-resistant PC-3 cells shows the clinical potential of WL-276 against HRPC that is resistant to conventional therapies. The anticancer activity of WL-276 was manifested in its suppression of PC-3-induced prostate tumor growth in vivo. The selective toxicity of WL-276 against drug-resistant PC-3 cells and its in vivo suppression of PC-3 prostate tumor growth suggest that WL-276 is a promising lead candidate for the development of Bcl-2 antagonists against drug-resistant HRPC.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-10606283,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-10860979,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-11175750,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-11245486,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-13678404,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-14678963,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-15297406,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-15634760,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-15657350,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-15713891,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-15897586,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-15902208,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-16794010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-17021642,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-17034116,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-17066097,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-17074501,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-17181155,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-17227711,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-17237035,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-17378545,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-17404601,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-17552510,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18519699-8971161
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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 |
Jun
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pubmed:issn |
1538-7445
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
68
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4377-83
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pubmed:dateRevised |
2011-5-10
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pubmed:meshHeading |
pubmed-meshheading:18519699-Animals,
pubmed-meshheading:18519699-Antineoplastic Agents,
pubmed-meshheading:18519699-Apoptosis,
pubmed-meshheading:18519699-Cell Division,
pubmed-meshheading:18519699-Cell Line, Tumor,
pubmed-meshheading:18519699-Drug Resistance, Neoplasm,
pubmed-meshheading:18519699-Humans,
pubmed-meshheading:18519699-Male,
pubmed-meshheading:18519699-Mice,
pubmed-meshheading:18519699-Mice, Nude,
pubmed-meshheading:18519699-Prostatic Neoplasms,
pubmed-meshheading:18519699-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:18519699-Sulfonamides,
pubmed-meshheading:18519699-Thiazoles
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pubmed:year |
2008
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pubmed:articleTitle |
WL-276, an antagonist against Bcl-2 proteins, overcomes drug resistance and suppresses prostate tumor growth.
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pubmed:affiliation |
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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