title: Antiproliferative activity of fucoidan was associated with the induction of apoptosis and autophagy in AGS human gastric cancer cells.
abstract: Fucoidan, a sulfated polysaccharide purified from brown algae, possesses a variety of pharmacologic effects, including antiinflammatory, antioxidant, and anticancer properties; however, the underlying action mechanisms are not completely understood. This study investigated the possible mechanisms through which fucoidan exerts its antiproliferative action in cultured AGS human gastric adenocarcinoma cells. We found that fucoidan effectively inhibits the growth of AGS cells by inducing autophagy, as well as apoptosis. Apoptosis by fucoidan treatment was associated with the downregulation of antiapoptotic Bcl-2 and Bcl-xL expression, loss of mitochondrial membrane potential, activation of caspases, and concomitant degradation of poly-(ADP-ribose) polymerase protein. In addition, the morphological study indicated a characteristic finding of autophagy, such as the formation of autophagosomes in fucoidan-treated AGS cells. Furthermore, markers of autophagy, namely, the conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II and increased beclin-1 accumulation, were observed. Overall, the present data suggest that fucoidan induces apoptotic and autophagic cell death, and both apoptotic and autophagic mechanisms contribute to the fucoidan-induced AGS cell death.
authors.affiliation: Department of Pharmacy, Pusan National University, Busan, Republic of Korea.
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Park
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Taek-Jeong
authors.initials: TJ
authors.lastname: Nam
authors.forename: Nam
authors.initials: N
authors.lastname: Deuk Kim
authors.forename: Yung
authors.initials: Y
authors.lastname: Hyun Choi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D015415:Biomarkers / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010588:Phagosomes / Q000187:drug effects / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; C491997:BECN1 protein, human; D000071186:Beclin-1; D015415:Biomarkers; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D011134:Polysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C007789:fucoidan; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases