title: Fucoidan derived from Undaria pinnatifida induces apoptosis in human hepatocellular carcinoma SMMC-7721 cells via the ROS-mediated mitochondrial pathway.
abstract: Fucoidans, fucose-enriched sulfated polysaccharides isolated from brown algae and marine invertebrates, have been shown to exert anticancer activity in several types of human cancer, including leukemia and breast cancer and in lung adenocarcinoma cells. In the present study, the anticancer activity of the fucoidan extracted from the brown seaweed Undaria pinnatifida was investigated in human hepatocellular carcinoma SMMC-7721 cells, and the underlying mechanisms of action were investigated. SMMC-7721 cells exposed to fucoidan displayed growth inhibition and several typical features of apoptotic cells, such as chromatin condensation and marginalization, a decrease in the number of mitochondria, and in mitochondrial swelling and vacuolation. Fucoidan-induced cell death was associated with depletion of reduced glutathione (GSH), accumulation of high intracellular levels of reactive oxygen species (ROS), and accompanied by damage to the mitochondrial ultrastructure, depolarization of the mitochondrial membrane potential (MMP, Δψm) and caspase activation. Moreover, fucoidan led to altered expression of factors related to apoptosis, including downregulating Livin and XIAP mRNA, which are members of the inhibitor of apoptotic protein (IAP) family, and increased the Bax-to-Bcl-2 ratio. These findings suggest that fucoidan isolated from U. pinnatifida induced apoptosis in SMMC-7721 cells via the ROS-mediated mitochondrial pathway.
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Yang
authors.forename: Peisheng
authors.initials: P
authors.lastname: Wang
authors.forename: Huaxin
authors.initials: H
authors.lastname: Wang
authors.forename: Qiaomei
authors.initials: Q
authors.lastname: Li
authors.forename: Hongming
authors.initials: H
authors.lastname: Teng
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Liu
authors.forename: Wenbo
authors.initials: W
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Zou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D044648:Undaria / Q000737:chemistry*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D011134:Polysaccharides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C007789:fucoidan; D020169:Caspases; D005978:Glutathione