Apoptosis induction by glycoprotein isolated from Laminaria japonica is associated with down-regulation of telomerase activity and prostaglandin E2 synthesis in AGS human gastric cancer cells

Glycoprotein isolated from Laminaria japonica (LJGP) is known to exhibit significant cytotoxic activity against human cancer cells; however, the mechanisms of its cytoxicity are poorly understood. In this study, we investigated further possible mechanisms by which LJGP exerts its anti-cancer action in cultured human gastric carcinoma AGS cells. LJGP treatment of AGS cells resulted in inhibition of growth and induction of apoptosis in a time- and concentration-dependent manner, as determined by MTT assay, fluorescence microscopy, and flow cytometry analysis. The increase in apoptosis was associated with up-regulation of pro-apoptotic Bax expression, down-regulation of anti-apoptotic Bc1-2 and IAP family members, and activation of caspase-3 and -9. LJGP treatment markedly down-regulated the activity of telomerase and expression of human telomerase reverse transcriptase, a main determinant of telomerase enzymatic activity, with inhibition of Sp1 and c-Myc expression in a concentration-dependent manner. Furthermore, LJGP treatment also caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E-2 synthesis. These results provide important new insights into the possible molecular mechanisms of the anti-cancer activity of LJGP.