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

Eun Ji Kim,So Young Park,Jung Han Yoon Park,Jae-Yong Lee

doi:10.1186/1471-230x-10-96

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.

Highlights

Fucoidan is a sulfated polysaccharide found in brown algae; it has been shown to exhibit a number of biological effects, including anti-tumor effects
The 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
Fucoidan inhibits the growth of HT-29 and HCT116 cells We initially assessed the effects of different concentrations (5, 10, 20 μg/mL) of fucoidan on the growth of HT-29 and HCT116 cells by measuring the viable cell numbers via MTT assays

Summary

Introduction

Fucoidan is a sulfated polysaccharide found in brown algae; it has been shown to exhibit a number of biological effects, including anti-tumor effects. We evaluated the effects of fucoidan on apoptosis in HT-29 and HCT116 human colon cancer cells. Early-stage colorectal cancer can be successfully treated surgically, advanced-stage colorectal cancer frequently recurs and becomes fatal, even in patients receiving combination chemotherapy [2]. Chemotherapeutic agents such as cisplatin are routinely used in the treatment of advancedstage colorectal cancer, but provide only minimal for credible assessments of the cancer chemopreventive qualities of these bioactive food components. To the best of our knowledge, the effects of fucoidan on the growth of colon cancer cells and its underlying mechanisms have yet to be determined in detail

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