Document Detail

Resveratrol suppresses growth of human ovarian cancer cells in culture and in a murine xenograft model: eukaryotic elongation factor 1A2 as a potential target.
MedLine Citation:
PMID:  19738051     Owner:  NLM     Status:  MEDLINE    
The eukaryotic elongation factor 1A2 (eEF1A2) is known to retain oncogenic potential and is recognized as a novel target for cancer prevention and therapy. Resveratrol (trans-3,4',5-trihydroxystilbene), a phytoalexin present in grapes, has been reported to possess chemopreventive and chemotherapeutic activities. In the present study, we examined the growth-inhibitory effects of resveratrol in human ovarian cancer PA-1 cells, considering eEF1A2 as a potential molecular target. Pretreatment with resveratrol attenuated proliferation of serum-starved PA-1 cells stimulated with insulin or serum. Resveratrol also activated caspase-9, -7, and -3 and induced apoptosis in PA-1 cells in the presence of insulin or serum. Insulin or serum stimulation of PA-1 cells resulted in the marked induction of eEF1A2, which was suppressed by pretreatment with resveratrol. Moreover, resveratrol inhibited insulin- or serum-induced soft-agar colony formation in eEF1A2-transfected NIH3T3 cells. An antibody array directed to assess the phosphorylation of protein kinases revealed that treatment with insulin or serum induced the phosphorylation of Akt in PA-1 cells. Pharmacologic inhibition of Akt with LY294002 abrogated insulin- or serum-induced eEF1A2 expression and increased the caspase-3 activity. In another experiment, i.p. administration of resveratrol retarded the growth of PA-1 cell xenograft and the expression of eEF1A2 in athymic nude mice in association with decreased bromodeoxyuridine positivity, reduced expression of proliferating cell nuclear antigen, increased the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and caspase-3 staining, and diminished CD31 positivity. Taken together, eEF1A2 may be considered as a potential molecular target for the antiproliferative effects of resveratrol in PA-1 ovarian cancer cells.
Mee-Hyun Lee; Bu Young Choi; Joydeb Kumar Kundu; Young Kee Shin; Hye-Kyung Na; Young-Joon Surh
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-08
Journal Detail:
Title:  Cancer research     Volume:  69     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-09-16     Completed Date:  2009-10-07     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7449-58     Citation Subset:  IM    
Department of Pharmacy, College of Pharmacy, and Cancer Research Institute, Seoul National University, Seoul, South Korea.
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MeSH Terms
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects
Cell Growth Processes / drug effects
Down-Regulation / drug effects
Insulin / pharmacology
Mice, Inbred BALB C
NIH 3T3 Cells
Ovarian Neoplasms / drug therapy*,  metabolism,  pathology
Peptide Elongation Factor 1 / biosynthesis*
Proto-Oncogene Proteins c-akt / antagonists & inhibitors,  metabolism
Stilbenes / pharmacology*
Xenograft Model Antitumor Assays
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/EEF1A2 protein, human; 0/Insulin; 0/Peptide Elongation Factor 1; 0/Stilbenes; EC Proteins c-akt; Q369O8926L/resveratrol

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