| The Bcl-2-Beclin 1 interaction in (-)-gossypol-induced autophagy versus apoptosis in prostate cancer cells. | |
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MedLine Citation:
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PMID: 20930561 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bcl-2 is a key dual regulator of autophagy and apoptosis, but how the level of Bcl-2 influences the cellular decision between autophagy and apoptosis is unclear. The natural BH3-mimetic (-)-gossypol preferentially induces autophagy in androgen-independent (AI) prostate cancer cells that have high levels of Bcl-2 and are resistant to apoptosis, whereas apoptosis is preferentially induced in androgen-dependent or -independent cells with low Bcl-2. (-)-Gossypol induces autophagy via blocking Bcl-2-Beclin 1 interaction at the endoplasmic reticulum (ER), together with downregulating Bcl-2, upregulating Beclin 1 and activating the autophagic pathway. Furthermore, (-)-gossypol-induced autophagy is Beclin 1- and Atg5-dependent. These results provide new insights into the mode of cell death induced by Bcl-2 inhibitors, which could facilitate the rational design of clinical trials by selecting patients who are most likely to benefit from the Bcl-2-targeted molecular therapy. |
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Authors:
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Jiqin Lian; David Karnak; Liang Xu |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural Date: 2010-11-16 |
Journal Detail:
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Title: Autophagy Volume: 6 ISSN: 1554-8635 ISO Abbreviation: Autophagy Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-16 Completed Date: 2011-03-02 Revised Date: 2011-11-18 |
Medline Journal Info:
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Nlm Unique ID: 101265188 Medline TA: Autophagy Country: United States |
Other Details:
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Languages: eng Pagination: 1201-3 Citation Subset: IM |
Affiliation:
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Department of Radiation Oncology, Division of Radiation and Cancer Biology, University of Michigan Medical School, Ann Arbor, MI, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Apoptosis Regulatory Proteins / metabolism* Autophagy / drug effects* Cell Line, Tumor Gossypol / pharmacology* Humans Male Membrane Proteins / metabolism* Models, Biological Prostatic Neoplasms / metabolism*, pathology* Protein Binding / drug effects Proto-Oncogene Proteins c-bcl-2 / metabolism* RNA, Small Interfering / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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CA121830/CA/NCI NIH HHS; CA128220/CA/NCI NIH HHS; CA134655/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/BECN1 protein, human; 0/Membrane Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Small Interfering; 303-45-7/Gossypol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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