Molecular and cellular biochemistry
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Mol. Cell. Biochem. · Jan 2011
Nobiletin, a citrus flavonoid, suppresses invasion and migration involving FAK/PI3K/Akt and small GTPase signals in human gastric adenocarcinoma AGS cells.
Nobiletin, a compound isolated from citrus fruits, is a polymethoxylated flavone derivative shown to have anti-inflammatory, antitumor, and neuroprotective properties. This study has investigated that nobiletin exerted inhibitory effects on the cell adhesion, invasion, and migration abilities of a highly metastatic AGS cells under non-cytotoxic concentrations. Data also showed nobiletin could inhibit the activation of focal adhesion kinase (FAK) and phosphoinositide-3-kinase/Akt (PI3K/Akt) involved in the downregulation of the enzyme activities, protein expressions, messenger RNA levels of matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-2 (MMP-9). ⋯ Otherwise, nobiletin-treated AGS cells showed tremendously decreased in the phosphorylation and degradation of inhibitor of kappaBα (IκBα), the nuclear level of NF-κB, and the binding ability of NF-κB to NF-κB response element. Furthermore, nobiletin significantly decreased the levels of phospho-Akt and MMP-2/9 in Akt1-cDNA-transfected cells concomitantly with a marked reduction in cell invasion and migration. These results suggest that nobiletin can reduce invasion and migration of AGS cells, and such a characteristic may be of great value in the development of a potential cancer therapy.
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Mol. Cell. Biochem. · Jan 2011
Cardioprotection by ischemic postconditioning is abolished in depressed rats: role of Akt and signal transducer and activator of transcription-3.
Ischemic postconditioning (IPC) represents one of the most effective cardioprotective strategies against myocardial ischemia/reperfusion. Depression is commonly present in patients with coronary heart disease. However, whether depression interferes with the cardioprotection of IPC during myocardial ischemia/reperfusion and their underlying mechanisms remain largely unknown. ⋯ However, these cardioprotective effects of IPC were not observed in depressed rats. In addition, IPC had no effects on the phosphorylation of AKT and STAT-3 at reperfusion in depressed hearts, although it markedly increased the phosphorylation of AKT and STAT-3 at reperfusion in non-depressed hearts. In conclusion, these data indicate that cardioprotection by IPC is abolished during myocardial ischemia/reperfusion in depressed rats, and the underlying mechanisms are probably related to the impaired activation of AKT and STAT-3 at reperfusion.