We extracted a glycoprotein from the brown alga Laminaria japonica (LJGP). We previously demonstrated that LJGP induced apop- tosis in HT-29 colon cancer cells via the Fas- and the mitochondrial signaling pathway, and...We extracted a glycoprotein from the brown alga Laminaria japonica (LJGP). We previously demonstrated that LJGP induced apop- tosis in HT-29 colon cancer cells via the Fas- and the mitochondrial signaling pathway, and cell-cycle arrest. However, its effect on the cell membrane remained unknown. In this study, we identified the involvement of matrix metalloproteinase (MMP), integrin, and Epi- thelial (E)-cadherin in LJGP-induced apoptosis in HT-29 cells. LJGP treatment increased the expression and activity of MMP-2 and MMP-9. Furthermore, LJGP decreased the expression of integrin αν, β3, β5, β6 and E- cadherin. Consistent with a decreased expression of E-cadherin, LJGP inhibited the Wnt signaling pathway. Moreover, activation of downstream molecules of integrin, including focal adhesion kinase (FAK), the Src family of protooncogenic tyrosine kinases, extracellular signal-related kinase (ERK), and phosphatidyl inositol 3 kinase (PI-3K) were also decreased. These findings suggest that LJGP-induced apoptosis of HT-29 cells involves possible ECM disruption and cell detachment, which are executed principally through the activation of MMPs and by a decrease of adhesion molecules, contributing to a down-regulation of the PI-3K, MAPK, and Wnt signaling pathways. Apoptosis induced by ECM disruption or cell detachment is also known as anoikis. We can say that LJGP induces anoikis in HT-29 cells.展开更多
文摘We extracted a glycoprotein from the brown alga Laminaria japonica (LJGP). We previously demonstrated that LJGP induced apop- tosis in HT-29 colon cancer cells via the Fas- and the mitochondrial signaling pathway, and cell-cycle arrest. However, its effect on the cell membrane remained unknown. In this study, we identified the involvement of matrix metalloproteinase (MMP), integrin, and Epi- thelial (E)-cadherin in LJGP-induced apoptosis in HT-29 cells. LJGP treatment increased the expression and activity of MMP-2 and MMP-9. Furthermore, LJGP decreased the expression of integrin αν, β3, β5, β6 and E- cadherin. Consistent with a decreased expression of E-cadherin, LJGP inhibited the Wnt signaling pathway. Moreover, activation of downstream molecules of integrin, including focal adhesion kinase (FAK), the Src family of protooncogenic tyrosine kinases, extracellular signal-related kinase (ERK), and phosphatidyl inositol 3 kinase (PI-3K) were also decreased. These findings suggest that LJGP-induced apoptosis of HT-29 cells involves possible ECM disruption and cell detachment, which are executed principally through the activation of MMPs and by a decrease of adhesion molecules, contributing to a down-regulation of the PI-3K, MAPK, and Wnt signaling pathways. Apoptosis induced by ECM disruption or cell detachment is also known as anoikis. We can say that LJGP induces anoikis in HT-29 cells.
