Important role of β1-integrin in fucoidan-induced apoptosis via caspase-8 activation.
Fucoidan induces apoptosis by activating caspase-8 in human MCF-7 breast cancer cells, but the detailed mechanism for this is not understood. We demonstrate here that fucoidan interacted with the cell surface, and silencing the β1-integrin gene expression inhibited fucoidan-induced apoptosis accompanied by caspase-8 activation. Fucoidan induced formation of the β1-integrin-caspase-8 complex. These data indicate that β1-integrin is an important factor for the cell-surface binding of fucoidan and plays an important role in fucoidan-induced apoptosis. Fucoidan also induced recruitment of caspase-8 to the β1-integrin intracellular domain, cleaved it into the activated protein by direct combination with β1-integrin, and induced apoptosis via the caspase cascade in MCF-7 cells.
Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, Japan. yamasakiy@cc.miyazaki-u.ac.jp
Yumi
Y
Yamasaki
Masao
M
Yamasaki
Hirofumi
H
Tachibana
Koji
K
Yamada
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D047468:Immunoprecipitation; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000235:genetics; D020349:Surface Plasmon Resonance
D000970:Antineoplastic Agents; D019012:Integrin beta1; D011134:Polysaccharides; D034741:RNA, Small Interfering; C007789:fucoidan; D053181:Caspase 8