Document Detail


The Bcl-2-Beclin 1 interaction in (-)-gossypol-induced autophagy versus apoptosis in prostate cancer cells.
MedLine Citation:
PMID:  20930561     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jiqin Lian; David Karnak; Liang Xu
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2010-11-16
Journal Detail:
Title:  Autophagy     Volume:  6     ISSN:  1554-8635     ISO Abbreviation:  Autophagy     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-16     Completed Date:  2011-03-02     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101265188     Medline TA:  Autophagy     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1201-3     Citation Subset:  IM    
Affiliation:
Department of Radiation Oncology, Division of Radiation and Cancer Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / 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:
CA121830/CA/NCI NIH HHS; CA128220/CA/NCI NIH HHS; CA134655/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
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
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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