Fucoidan induces apoptosis of human HS-Sultan cells accompanied by activation of caspase-3 and down-regulation of ERK pathways

Fucoidan induces apoptosis of human HS-Sultan cells accompanied by activation of caspase-3 and down-regulation of ERK pathways
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DOI:
10.1002/ajh.20182
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发表时间:
2005-01-01
影响因子:
12.8
通讯作者:
Kizaki, M
Kizaki, M
中科院分区:
医学1区
文献类型:
--
作者:
Aisa, Y;Miyakawa, Y;Kizaki, M

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Fucoidan, a sulfated polysaccharide in brown seaweed, was found to inhibit proliferation and induce apoptosis in human lymphoma HS-Sultan cell lines. Fucoidan-induced apoptosis was accompanied by the activation of caspase-3 and was partially prevented by pretreatment with a pan-caspase inhibitor, z-VAD-FMK. The mitochondrial potential in HS-Sultan cells was decreased 24 hr after treatment with fucoidan, indicating that fucoidan induced apoptosis through a mitochondrial pathway. When HS-Sultan was treated with 100 mug/mL fucoidan for 24 hr, phosphorylation of ERK and GSK markedly decreased. In contrast, phosphorylation of p38 and Akt was not altered by treatment with fucoidan. L-Selectin and P-selectin are known to be receptors of fucoidan; however, as HS-Sultan does not express either of these selectins, it is unlikely that fucoidan induced apoptosis through them in HIS-Sultan. The neutralizing antibody, Dreg56, against human L-selectin did not prevent the inhibitory effect of fucoidan on the proliferation of IM9 and MOLT4 cells, both of which express L-selectin; thus it is possible fucoidan induced apoptosis though different receptors. These results demonstrate that fucoidan has direct anticancer effects on human HS-Sultan cells through caspase and ERK pathways. (C) 2004 Wiley-Liss, Inc.