Linked Life Data

19738414

Source:http://linkedlifedata.com/resource/pubmed/id/19738414

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-10-19
pubmed:abstractText
Tamoxifen (Tx) interacts with high affinity to the microsomal antiestrogen binding site (AEBS) which is a hetero-oligomeric complex involved in cholesterol metabolism. We established that Tx and other AEBS ligands induce breast cancer cell differentiation, apoptosis and autophagy through the induction of sterol accumulation. We determined that cell death is sterol- and ROS-dependent and is prevented by the antioxidant vitamin E. Macroautophagy is characterized by the accumulation of autophagic vacuoles, an increase in the expression of Beclin 1 and the stimulation of autophagic flux. We established that macroautophagy is sterol-dependent and is associated with cell survival rather than cytotoxicity, since blockage of macroautophagy sensitizes cells to AEBS ligands. These results show that the accumulation of sterols by AEBS ligands in MCF-7 cells induces both apoptosis and macroautophagy. Collectively, these data support a therapeutic potential for selective AEBS ligands in breast cancer management and reveal a mechanism that explains the induction of autophagy in MCF-7 cells by Tx and other selective estrogen receptor modulators. Moreover these data give pharmacological clues to improve the apoptotic efficacy of AEBS ligands.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1554-8635
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1066-7
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Tamoxifen and AEBS ligands induced apoptosis and autophagy in breast cancer cells through the stimulation of sterol accumulation.
pubmed:affiliation
Affichem, Toulouse, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't