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rdf:type |
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lifeskim:mentions |
umls-concept:C0010749,
umls-concept:C0018096,
umls-concept:C0030685,
umls-concept:C0205263,
umls-concept:C0376515,
umls-concept:C0391871,
umls-concept:C0392747,
umls-concept:C0443172,
umls-concept:C0680255,
umls-concept:C1283071,
umls-concept:C1326205,
umls-concept:C1963578
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pubmed:issue |
12
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pubmed:dateCreated |
2006-10-2
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pubmed:abstractText |
Cells without Bak and Bax are largely resistant to apoptosis, despite the presence of other key components of the apoptotic machinery. We screened 7,800 natural compounds and found several that could specifically induce caspase activation and the release of cytochrome c (cyto c) in the bak(-/-)/bax(-/-) cells. One of these was gossypol, a polyphenolic compound naturally found in cottonseed that has been used in antifertility trials. We found that gossypol, but not other Bcl-2-interacting molecules, induced cyto c release and loss of mitochondrial membrane potential (delta psi m) independently of mPTP and Bak/Bax activation. Furthermore, we found that gossypol induced an allosteric change in Bcl-2 in both bak(-/-)/bax(-/-) cells and Bcl-2 overexpressing cells. This change in Bcl-2 conformation led to the release of cyto c in the presence of Bcl-2 and Bcl-xL in reconstituted proteoliposomes. We also observed that gossypol substantially reduced the growth of tumor xenografts from Bcl-2 overexpressing cells in nude mice. We conclude that gossypol converts the antiapoptotic molecule Bcl-2 into a proapoptotic molecule that can mediate the release of cyto c and induce apoptosis.
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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 |
Oct
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pubmed:issn |
1530-6860
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pubmed:author |
pubmed-author:ChenQuanQ,
pubmed-author:ChenYingyuY,
pubmed-author:DuGuanhuaG,
pubmed-author:HaoXiaojiangX,
pubmed-author:HeHongpingH,
pubmed-author:LeiXiaoboX,
pubmed-author:LiaoXudongX,
pubmed-author:MaoJianhuaJ,
pubmed-author:MehrpourMaryamM,
pubmed-author:QuHongH,
pubmed-author:TyoJ SJS,
pubmed-author:WangXiaohuiX,
pubmed-author:YuWenyuW,
pubmed-author:ZongWeixingW
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pubmed:issnType |
Electronic
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2147-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16935937-Animals,
pubmed-meshheading:16935937-Antineoplastic Agents,
pubmed-meshheading:16935937-Apoptosis,
pubmed-meshheading:16935937-Cytochromes c,
pubmed-meshheading:16935937-Gossypol,
pubmed-meshheading:16935937-Liposomes,
pubmed-meshheading:16935937-Mice,
pubmed-meshheading:16935937-Mice, Inbred BALB C,
pubmed-meshheading:16935937-Mice, Knockout,
pubmed-meshheading:16935937-Mice, Nude,
pubmed-meshheading:16935937-Neoplasms, Experimental,
pubmed-meshheading:16935937-Protein Conformation,
pubmed-meshheading:16935937-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:16935937-Tumor Burden,
pubmed-meshheading:16935937-bcl-2-Associated X Protein,
pubmed-meshheading:16935937-bcl-X Protein
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pubmed:year |
2006
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pubmed:articleTitle |
Gossypol induces Bax/Bak-independent activation of apoptosis and cytochrome c release via a conformational change in Bcl-2.
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pubmed:affiliation |
The Laboratory of Apoptosis and Cancer Biology, Institute of Zoology, Chinese Academy of Sciences, Bei Si Huan Xi Road 25, Haidian District, Beijing 100080, PR China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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