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 H(2)O(2) in human adenocarcinoma gastric cells (AGS) and we evaluate the anti-proliferative action of the natural stilbene trans-resveratrol. We demonstrate that H(2)O(2) 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 H(2)O(2)-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.
Aquilano
Katia
K
Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy.
Baldelli
Sara
S
Rotilio
Giuseppe
G
Ciriolo
Maria Rosa
MR
D000230:Adenocarcinoma / Q000473:pathology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000473:pathology*
D017382:Reactive Oxygen Species; D013267:Stilbenes; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; D000077185:Resveratrol