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Resveratrol suppresses growth of human ovarian cancer cells in culture and in a murine xenograft model: Eukaryotic elongation factor 1A2 as a potential target

Cited 59 time in Web of Science Cited 65 time in Scopus
Authors
Lee, Mee-Hyun; Choi, Bu Young; Kundu, Joydeb Kumar; Shin, Young Kee; Na, Hye-Kyung; Surh, Young-Joon
Issue Date
2009-09
Publisher
AMER ASSOC CANCER RESEARCH
Citation
Cancer Research, Vol.69 No.18, pp.7449-7458
Abstract
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 he considered as a potential molecular target for the antiproliferative effects of resveratrol in PA-1 ovarian cancer cells. [Cancer Res 2009;69(18):7449-58]
ISSN
0008-5472
Language
English
URI
https://hdl.handle.net/10371/80932
DOI
https://doi.org/10.1158/0008-5472.CAN-09-1266
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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