Fucoidan Preferentially Induces the Mitochondrial Pathway- Mediated Cell Death in Hematopoietic Malignant Cells

Fucoidan is a sulfated polysaccharide that occurs at high levels in some seaweed and in the eggs of sea urchin and bodies of sea cucumbers. Uptake of fucoidan-rich food is suggested to be one of the causes of longevity in Japan. Fucoidan shows anti-coagulant, antivirus, anti-inflammatory, anti-tumor and other various favorable biological activities both in vitro and in vivo. In this study, the cell death induction activities of fucoidan were investigated using eight different human cancer as well as normal cell lines at the cellular and molecular levels. Two hematopoietic cell lines, Jurkat and K562, showed maximum sensitivities against fucoidan. Fucoidan at 100 μg/ml induced cell death of Jurkat cells. To further investigate the cell death induction mechanism of fucoidan against hematopoietic cell lines, we detected membrane turnover activities by annexin-V assay and detected active caspases by western blotting. An annexin-V assay indicated higher apoptosis induction activities in Jurkat cells. Higher inductions of executioner caspases, caspase-3, -6, and -7 were also observed in Jurkat cells. In particular, the activation of caspase-6 was relatively high and detected 12 hours after fucoidan treatment. Treatment with inhibitors against pan caspases and caspase-9 showed significant reduction effects on fucoidan-induced cell death. An apparent decrease of mitochondrial membrane potential was observed in both of the hematopoietic cell lines. These results strongly suggest the involvement of a mitochondrial apoptotic pathway by fucoidan in hemaotopoietic cells. _____________________________________________________________________________________________________________