Fucoidan is a sulfated polysaccharide found in edible brown algae, such as Undaria pinnatifida, Fucus vesiculosus and Ecklonia cava. Fucoidan usually contains a large proportion of L-fucose and sulfate. Fucoidan has been reported to show various biological activities such as anti-tumor, [1][2][3][4] anti-coagulant, 5,6) anti-viral, 7) and anti-inflammatory. 8) Furthermore, its anti-tumor activity may be due to the inhibition of tumor angiogenesis in Ehrlich ascites carcinoma 1) and lung carcinoma, 9) as well as the direct induction of apoptosis in U9373) and HS-sultan cells. 4) Several marine algal polysaccharides, fucoidan in particular, have been found to induce apoptosis in cancer cells. [10][11][12] Nevertheless, there is no report on the effect of fucoidan in colon cancer, one of the most malignant neoplasias and a frequently occurring tumor in the world.Recently, it has been demonstrated that the phosphorylation/de-phosphorylation states of some regulatory proteins are crucial events along the pathways controlling cell growth and apoptosis. A well-established apoptotic signaling cascade is regulated by mitogen activated protein (MAP) kinases.13) The MAPK pathway consists of a three-tiered kinase core where MAP3K activates an MAP2K which in turn activates an MAPK (ERK, JNK; c-Jun N-terminal kinase, and p38), resulting in the activation of nuclear factor-kB (NF-kB) and cell survival.14,15) Akt signaling is another important transduction pathway that plays a critical role in controlling the balance between cell survival and apoptosis. 16) In this study, we investigated the effect of fucoidan on the induction of apoptosis in HCT-15 cells, human colon adenocarcinoma cells. Because MAPK and PI3K/Akt pathways are involved in cellular proliferation, differentiation, and apoptosis, [17][18][19][20] the phosphorylation and activities of two MAPKs, ERK and p38 MAPK as well as Akt were investigated. Understanding of the underlying mechanism of the induction of apoptosis by fucoidan will benefit the development of chemopreventive and/or chemotherapeutics for colon cancer. MATERIALS AND METHODS Fucoidan and Diallyl DisulfideFucoidan (from Fucus vesiculosus) and diallyl disulfide (DADS) were purchased from Sigma (St. Louis, MO, U.S.A.). The fucoidan was dissolved in phosphate-buffered saline (PBS; Sigma, St. Louis, MO, U.S.A.) to 50 mg/ml and the DADS was dissolved in dimethylsulfoxide (DMSO; Sigma, St. Louis, MO, U.S.A.) to 50 mM at Ϫ20°C until further use.Cell Culture The HCT-15 human colon cancer cells were purchased from the Korea Cell Line Bank (KCLB) and cultured in RPMI1640 (Gibco BRL, Grand Island, NY, U.S.A.) medium supplemented with 10% fetal bovine serum (FBS) (Gibco BRL, Grand Island, NY, U.S.A.) at 37°C in a 5% CO 2 atmosphere. The exponentially growing cells were used throughout the experiments.MTT Assay The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) (Sigma, Saint Louis, MO, U.S.A.) assay was performed as previously described. 21) In brief, HCT-15 cells were cultured in a 96-well pla...

Fucoidan, a sulfated polysaccharide, has a variety of biological activities, such as anti-cancer, anti-angiogenic and anti-inflammatory. However, the mechanisms of action of fucoidan as an anti-cancer agent have not been fully elucidated. The present study examined the anti-cancer effect of fucoidan obtained from Undaria pinnatifida in PC-3 cells, human prostate cancer cells. Fucoidan induced the apoptosis of PC-3 cells by activating both intrinsic and extrinsic pathways. The induction of apoptosis was accompanied by the activation of extracellular signal-regulated kinase mitogen-activated protein kinase (ERK1/2 MAPK) and the inactivation of p38 MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt. In addition, fucoidan also induced the up-regulation of p21Cip1/Waf and down-regulation of E2F-1 cell-cycle-related proteins. Furthermore, in the Wnt/β-catenin pathway, fucoidan activated GSK-3β that resulted in the decrease of β-catenin level, followed by the decrease of c-myc and cyclin D1 expressions, target genes of β-catenin in PC-3 cells. These results suggested that fucoidan treatment could induce intrinsic and extrinsic apoptosis pathways via the activation of ERK1/2 MAPK, the inactivation of p38 MAPK and PI3K/Akt signaling pathway, and the down-regulation of Wnt/β-catenin signaling pathway in PC-3 prostate cancer cells. These data support that fucoidan might have potential for the treatment of prostate cancer.

Fucoidan, a sulfated polysaccharide, has various biological activities, such as anticancer, antiangiogenic and antiinflammatory effects; however, the mechanisms of action of fucoidan on anticancer activity have not been fully elucidated. The anticancer effects of fucoidan from Undaria pinnatifida on A549 human lung carcinoma cells were examined. Treatment of A549 cells with fucoidan resulted in potent antiproliferative activity. Also, some typical apoptotic characteristics, such as chromatin condensation and an increase in the population of sub-G1 hypodiploid cells, were observed. With respect to the mechanism underlying the induction of apoptosis, fucoidan reduced Bcl-2 expression, but the expression of Bax was increased in a dose-dependent manner compared with the controls. Furthermore, fucoidan induced caspase-9 activation, but decreased the level of procaspase-3. Cleavage of poly-ADP-ribose polymerase (PARP), a vital substrate of effector caspase, was found. The study further investigated the role of the MAPK and PI3K/Akt pathways with respect to the apoptotic effect of fucoidan, and showed that fucoidan activates ERK1/2 in A549 cells. Unlike ERK1/2, however, treatment with fucoidan resulted in the down-regulation of phospho-p38 expression. In addition, fucoidan resulted in the down-regulation of phospho-PI3K/Akt. Together, these results indicate that fucoidan induces apoptosis of A549 human lung cancer cells through down-regulation of p38, PI3K/Akt, and the activation of the ERK1/2 MAPK pathway.

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