Fucoidan present in brown algae induces apoptosis of human colon cancer cells

Abstract

BackgroundFucoidan is a sulfated polysaccharide found in brown algae; it has been shown to exhibit a number of biological effects, including anti-tumor effects. In this study, we evaluated the effects of fucoidan on apoptosis in HT-29 and HCT116 human colon cancer cells.MethodsHT-29 and HCT116 cells were cultured with various concentrations of fucoidan (0 - 20 μg/mL). Apoptosis was assayed via Hoechst staining and Annexin V staining followed by flow cytometric analysis. Western blot analyses and JC-1 staining were conducted to determine the levels of apoptosis-regulating proteins and mitochondrial membrane permeability, respectively.ResultsFucoidan induced substantial reductions in viable cell numbers and apoptosis of HT-29 and HCT116 cells in a dose-dependent manner. In HT-29 cells, fucoidan also increased the levels of cleaved caspases-8, -9, -7, and -3, and cleaved poly (ADP-ribose) polymerase (PARP) levels. The levels of the X-linked inhibitor of apoptosis protein and survivin were attenuated in the fucoidan-treated cells. Fucoidan was also shown to enhance mitochondrial membrane permeability, as well as the cytochrome c and Smac/Diablo release from the mitochondria. Fucoidan increased the levels of the Bak and truncated Bid proteins, but reduced the levels of Mcl-1. Additionally, fucoidan increased the levels of the tumor necrosis factor-related apoptosis-inducing ligand, Fas and death receptor 5 proteins. The caspase-8 and -9 inhibitors Z-IETD-FMK and Z-LEHD-FMK induced a reduction in fucoidan-mediated apoptosis. Caspase-8 inhibitor inhibited the fucoidan-induced cleavage of Bid, caspases-9 and -3, and PARP.ConclusionThe findings of this study indicate that fucoidan induces apoptosis in HT-29 and HCT116 human colon cancer cells, and that this phenomenon is mediated via both the death receptor-mediated and mitochondria-mediated apoptotic pathways. These results suggest that fucoidan may prove useful in the development of a colon cancer-preventive protocol.

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.…”

Anti-inflammatory actions of plant-derived multiple monoclonal antibody CO17-1A × BR55 related with anti-cancer effects in AOM/DSS-induced colorectal cancer mouse via down-regulating of ERK1/2

“…The previous study described that caspases are classified based on either initiator or effector caspases in apoptosis (Kim et al 2010). Initiator caspases, caspase-8 and -9, are phosphorylated by a variety apoptotic signals (Kim et al 2010). Activated or cleaved caspase-3 is an essential effector for induction of apoptosis (Xue et al 2012).…”

“…Bax gene product dimerizes with Bcl-2 and controls cell death by activating caspase-3 (Seol et al 2001). The previous study described that caspases are classified based on either initiator or effector caspases in apoptosis (Kim et al 2010). Initiator caspases, caspase-8 and -9, are phosphorylated by a variety apoptotic signals (Kim et al 2010).…”

“…Moreover, antitumor and anti-inflammatory effects of multiple mAb P CO17-1A × BR55 were significantly better than anti-EpCAM and mAb P CO17-1A alone. Chemopreventive/chemotherapeutic agent can reduce the overall growth of cancer cells by apoptosis (Kim et al 2010). .…”

Low molecular fucoidan and its macromolecular complex with bee venom melittin

“…Molecular mass of fucoidan is heterogenic (10 -1000 kDa) and difficult for making measurement standards in studying of its biological activity. The molecular mechanism of fucoidan's anti-tumor [2], LDL cholesterol lowering [3], blood anti-coagulating [4], anti-oxidant and anti-inflammatory [5], anti-viral [6] and contraceptive [7] activities have not yet been revealed in detail. It has been reported that fucoidan is absorbed in an undigested form and displays thereafter all beneficial activities.…”