In this study, we investigated whether the inhibition of endogenous phosphorylation of mitogen-activated protein kinase (MAPK) and diallyl disulfide (DADS)-induced phosphorylation of MAPKs with MAPK specific inhibitors, SB203580 and U0126 (for phospho-p38 and phospho-p42/p44, respectively), can induce or enhance apoptosis in human CNE2 nasopharyngeal carcinoma cells. Our data demonstrate that MAPK inhibitors decrease the viability of CNE2 cells, stimulate typical apoptotic morphologic changes, and enhance DADS-induced apoptosis. The present findings indicate that phosphorylation of MAPKs plays an important cytoprotective role in CNE2 cell apoptosis and the DADS-induced apoptotic process.

Abstract. The adipocyte-derived hormone leptin is associated with hypertension. The involvement of cyclooxygenase-2 (COX-2) and its downstream vasomotor products prostaglandin (PG) and thromboxane (TX)A 2 in the mechanisms of action of leptin have remained elusive. The aim of the present study was to investigate the effects of leptin on the expression of COX-2 by rat aortic endothelial cells (RAECs) and the concentration of its products, represented by 6-keto PGF 1α and TXB 2 , in the culture media. RAECs were isolated, cultured and identified by immunofluorescence staining. The RAECs were incubated with different concentrations of leptin (10 -10 , 10 -9 and 10 -8 M) for various durations (36 or 48 h). COX-2 mRNA and protein expression in the cells was detected by reverse-transcription quantitative PCR and western blot analysis, respectively. The vasodilator 6-keto PGF 1α and the vasoconstrictor TXB 2 were detected in the supernatant by ELISA. The cultured cells displayed specific factor VIII expression in the cytoplasm. Compared with the PBS-treated control group, leptin significantly increased the expression of COX-2 mRNA and protein in a time-and dose-dependent manner (P<0.01). Furthermore, the vasodilator 6-keto PGF 1α was increased and the TXB 2 /6-keto PGF 1α ratio decreased only with relatively high concentrations of leptin (10 -9 or 10 -8 M; P<0.01), but TXB 2 levels were not affected (P>0.05). In conclusion, leptin significantly increased the expression of inflammatory marker COX-2 and its downstream product 6-keto PGF 1α , while also decreasing the TXB 2 /6-keto PGF 1α ratio in vitro. These observations suggested that COX-2 may have an important role in the effects of leptin on inflammation, such as the low-inflammatory disease hypertension. However, selective COX-2 inhibitors may increase the risk of hypertension due to inhibiting 6-keto PGF 1α , the vasodilator product of COX-2.