trans-Resveratrol inhibits H2O2-induced adenocarcinoma gastric cells proliferation via inactivation of MEK1/2-ERK1/2-c-Jun signalling axis

In this report we investigate the signalling pathway activated by H₂O₂ in human adenocarcinoma gastric cells (AGS) and we evaluate the anti-proliferative action of the natural stilbene trans-resveratrol. We demonstrate that H₂O₂ accelerates cell growth and induces a prompt MEK1/2-ERK1/2 activation. Such events are also associated with the activation of c-Jun and its translocation into the nuclear compartment. A specific inhibitor of ERK1/2 phosphorylation by MEK1/2 (U0126) abrogates these phenomena. On the contrary, specific inhibition of JNK activity does not influence H₂O₂-mediated growth, suggesting that cell proliferation likely proceeds via MEK1/2-ERK1/2-Jun signalling axis. trans-Resveratrol is also able to completely suppress the increase in proliferation. We demonstrate that this property is not due to its antioxidant capacity but rather due to a specific inhibition of ERK1/2 phosphorylation by MEK1/2 and repression of c-Jun activation.