Low Molecular Weight Mannogalactofucans Derived from <Emphasis Type="Italic">Undaria pinnatifida</Emphasis> Induce Apoptotic Death of Human Prostate Cancer Cells In Vitro and In Vivo |
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Authors: | Jisun Lee Seul Lee Andriy Synytsya Peter Capek Chang Won Lee Ji Won Choi Sarang Cho Woo Jung Kim Yong Il Park |
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Institution: | 1.Department of Biotechnology,The Catholic University of Korea,Bucheon,South Korea;2.Department of Carbohydrate Chemistry and Technology,University of Chemical Technology in Prague,Prague 6,Czech Republic;3.Institute of Chemistry, Centre for Glycomics,Slovak Academy of Sciences,Bratislava,Slovakia;4.Biocenter, Gyeonggido Business and Science Accelerator (GBSA),Suwon,South Korea |
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Abstract: | Low molecular weight mannogalactofucans (LMMGFs) prepared by enzymatic degradation of high molecular weight Undaria galactofucan (MF) were evaluated for their anti-cancer effects against human prostate cancer. Correlation NMR and linkage analyses confirmed that LMMGFs consist mainly of α-fucose and β-galactose units: α-fucose units are 1,3-linked; β-galactose units are terminal, 1,3- and/or 1,6-linked; both sugars are partially sulphated, fucose at positions O-2 and/or O-4 and galactose at O-3. Mannose residue, as a minor sugar, presents as the 1,4-linked terminal units. LMMGFs more significantly induced cell cycle arrest at the G0/G1 phase and cell death via suppression of the Akt/GSK-3β/β-catenin pathway than MF in human PC-3 prostate cancer cells. LMMGFs upregulated mRNA expression of death receptor-5 (DR-5), the ratio of Bax to Bcl-2, the cleavage of caspases and PARP, the depolarisation of mitochondrial membrane potential, and ROS generation. LMMGFs (200–400 mg/kg) effectively reduced both tumour volume and size in a xenografted mouse model. These results demonstrated that LMMGFs attenuate the growth of human prostate cancer cells both in vitro and in vivo, suggesting that LMMGFs can be used as a potent functional ingredient in health-beneficial foods or as a therapeutic agent to prevent or treat androgen-independent human prostate cancer. |
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