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

Abstract

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 mg/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 HS-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. Am.

Effects of sulfated fucan, ascophyllan, from the brown Alga Ascophyllum nodosum on various cell lines: A comparative study on ascophyllan and fucoidan

“…Although the exact cytotoxic mechanisms of these sulfated polysaccharides are still unclear, it has been reported that fucoidan was able to induce apoptotic cell death in the human lymphoma HS-Sultan cell line through the activation of caspase-3 (20). Our recent study has demonstrated that ascophyllan also induces apoptosis in U937 cells, as judged by typical apoptotic nuclear morphological changes and DNA fragmentation (14).…”

Fucoidan induces Apoptosis in MDA-MB-231 Cells by Activating Caspase Cascade and Down-regulating XIAP

“…A number of genes that are associated with apoptotic cell death were tested in order to clarify the mechanism by which fucoidan treatment induces apoptosis in MDA-MB-231 cells. According to some previously conducted studies, caspases act as key players of fucoidan-induced apoptosis [20][21][22][23][24][25][26][27] . These findings have guided the researcher to propose a model in which fucoidan promotes apoptosis in MDA-MB-231 cells through increasing caspases activity.…”

Biological Activities of Fucose-Containing Polysaccharide Ascophyllan Isolated from the Brown AlgaAscophyllum nodosum

“…Recent study has demonstrated that a commercially available fucoidan (Sigma, St. Louis, MO) purified from Fucus vesiculosus induced apoptosis in human myeloma and leukemia cells through activation of the caspase-3 and down-regulation of ERK pathways. 16) In addition, Riou et al reported that fucoidan extract obtained from Ascophyllum nodosum directly inhibited the proliferation of a human non-small cell lung cancer cell line (NSLC-N6). 17) Thus, it seems likely that sulfated fucans like fucoidans and ascophyllan are able to cause direct cytotoxic effects on target cells, including tumor cells, through induction of apoptosis.…”