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 Bcl-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 E2 synthesis. These results provide important new insights into the possible molecular mechanisms of the anti-cancer activity of LJGP.
Department of Biomaterial Control and Blue-Bio Industry Regional Innovation Center, Dongeui University Graduate School, Busan 614-714, Republic of Korea.
Min Ho
MH
Han
Gi Young
GY
Kim
Sung-Kwon
SK
Moon
Wun-Jae
WJ
Kim
Taek-Jeong
TJ
Nam
Yung Hyun
YH
Choi
D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015536:Down-Regulation; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007795:Laminaria / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000473:pathology*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D006023:Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C509186:TERT protein, human; D019098:Telomerase; D053148:Caspase 3; D015232:Dinoprostone