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Resveratrol enhances anti-proliferative effect of VACM-1/cul5 in T47D cancer cells.
MedLine Citation:
PMID:  20949323     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Vasopressin-activated calcium-mobilizing (VACM-1) protein is a cul-5 gene product that forms complexes with a subclass of ubiquitin E3 ligases involved in proteasomal protein degradation. The expression of VACM-1 cDNA in the T47D breast cancer cell line inhibits growth and decreases phosphorylation of mitogen activated protein kinase. Factors that regulate expression or stability of VACM-1 protein have not been identified, however. In our search to identify drugs/substances that may control VACM-1 protein expression, we examined the effects of resveratrol (trans-3,5,4'-trihydroxystilbene), a natural component in the human diet which inhibits tumor initiation and promotion. CMV vector and VACM-1 cDNA stably transfected T47D breast cancer-derived cells were treated with resveratrol and cell growth and VACM-1 protein concentrations were measured. Since the cellular mechanism of resveratrol-dependent inhibition of cell growth also involves the regulation of estrogen receptors, the effect of 17-β-estradiol and resveratrol on ERα levels and on cell growth was examined in control and in VACM-1 cDNA transfected cells. Our results demonstrate that antiproliferative effect of resveratrol observed in the control T47D cancer cells was significantly enhanced in VACM-1 cDNA transfected T47D cells. Western blot results indicated that resveratrol increased VACM-1 protein concentration. Finally, treatment with resveratrol for 24 and 48 h attenuated 17-β-estradiol induced increase in cell growth both in control and in VACM-1 cDNA transfected cells. The effect was significantly higher in the VACM-1 cDNA transfected cells when compared to controls. These results indicate that the antiproliferative effect of resveratrol may involve induction of VACM-1/cul5.
Authors:
Justin Lubbers; Steven Lewis; Emily Harper; Michael P Hledin; Gabriel A Marquez; Alyssa E Johnson; Danelle R Graves; Maria A Burnatowska-Hledin
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Publication Detail:
Type:  Journal Article     Date:  2010-10-15
Journal Detail:
Title:  Cell biology and toxicology     Volume:  27     ISSN:  1573-6822     ISO Abbreviation:  Cell Biol. Toxicol.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8506639     Medline TA:  Cell Biol Toxicol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  95-105     Citation Subset:  IM    
Affiliation:
Departments of Biology and Chemistry, Hope College, Holland, MI, 49422-9000, USA.
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