| Resveratrol suppresses growth of human ovarian cancer cells in culture and in a murine xenograft model: eukaryotic elongation factor 1A2 as a potential target. | |
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MedLine Citation:
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PMID: 19738051 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Mee-Hyun Lee; Bu Young Choi; Joydeb Kumar Kundu; Young Kee Shin; Hye-Kyung Na; Young-Joon Surh |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-09-08 |
Journal Detail:
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Title: Cancer research Volume: 69 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-09-16 Completed Date: 2009-10-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 7449-58 Citation Subset: IM |
Affiliation:
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Department of Pharmacy, College of Pharmacy, and Cancer Research Institute, Seoul National University, Seoul, South Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents, Phytogenic / pharmacology* Apoptosis / drug effects Cell Growth Processes / drug effects Down-Regulation / drug effects Female Humans Insulin / pharmacology Mice 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 |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Phytogenic; 0/EEF1A2 protein, human; 0/Peptide Elongation Factor 1; 0/Stilbenes; 11061-68-0/Insulin; 501-36-0/resveratrol; EC 2.7.1.37/Proto-Oncogene Proteins c-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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