Fucoidan induces apoptosis of human HS-sultan cells accompanied by activation of caspase-3 and down-regulation of ERK pathways.
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 microg/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 anti-cancer effects on human HS-Sultan cells through caspase and ERK pathways.
Aisa
Yoshinobu
Y
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Miyakawa
Yoshitaka
Y
Nakazato
Tomonori
T
Shibata
Hideyuki
H
Saito
Kaori
K
Ikeda
Yasuo
Y
Kizaki
Masahiro
M
D000906:Antibodies / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D038341:Glycogen Synthase Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D018021:Lithium Chloride / Q000494:pharmacology; D008223:Lymphoma / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology; D019007:P-Selectin / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D015398:Signal Transduction
D000906:Antibodies; D000970:Antineoplastic Agents; D019007:P-Selectin; D011134:Polysaccharides; D019041:L-Selectin; C007789:fucoidan; D038341:Glycogen Synthase Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D018021:Lithium Chloride