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.