Activation of caspase-8 contributes to fucoidan-induced apoptosis in HT-29 human colon cancer cells

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 ...