Apoptosis Inducing Activity of Fucoidan in HCT-15 Colon Carcinoma Cells

Abstract

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...

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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.…”

Effects of polysaccharides derived from Orostachys japonicus on induction of cell cycle arrest and apoptotic cell death in human colon cancer cells

“…In a previous study, we reported the anti-cancer activity of polysaccharides from Salicornia herbacea in HT-29 cells (8). Other investigators have also demonstrated that polysaccharides exhibit these suppressive effects on several cancer cells (11)(12)(13).…”