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Activation of caspase‐8 contributes to fucoidan‐induced apoptosis in HT‐29 human colon cancer cells
Author(s) -
Kim Eun Ji,
Park So Young,
Park Hee Sook,
Hong Ji Eun,
Sin Min Jeong,
Shin HyunKyung,
Kwon Dae Young,
Surh YoungJoon,
Park Jung Han Yoon
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a50-c
Subject(s) - fucoidan , apoptosis , xiap , cytochrome c , poly adp ribose polymerase , caspase , survivin , chemistry , microbiology and biotechnology , caspase 8 , caspase 3 , biology , programmed cell death , biochemistry , polysaccharide , enzyme , polymerase
Fucoidan is a sulfated polysaccharide from the brown alga, Fucus vesiculous and has been reported to inhibit tumor angiogenesis. The present study examined fucoidan‐mediated apoptosis in the HT‐29 human colon cancer cell line. Fucoidan substantially decreased viable HT‐29 cell numbers and increased apoptotic cell numbers in a dose‐dependent manner (0 – 20 μ g/mL). Western blot analyses of total cell lysates revealed that fucoidan increased the levels of cleaved caspase‐8, ‐9, ‐7, and ‐3, and poly(ADP‐ribose) polymerase (PARP). Fucoidan increased the levels of the proapoptotic protein Bak and truncated Bid. In addition, fucoidan increased the translocation of cytochrome c and Smac/Diablo from the mitochondria to the cytoplasm. The levels of X‐linked inhibitor of apoptosis protein (XIAP) and survivin were decreased by treatment of fucoidan. The caspase‐8 inhibitor Z‐IETD‐FMK attenuated the fucoidan‐induced activation of caspases‐8 and ‐3, increase in tBid, PARP cleavage, and apoptosis. We have demonstrated that the induction of apoptosis by fucoidan in HT‐29 human colon cancer cells may be mediated via the activation of the caspase‐8 pathway leading to changes in mitochondrial events, which are associated with cytochrome c and Smac/Diablo release and subsequent activation of the caspase‐9/caspase‐3 cascade