title: Induction of apoptosis by fucoidan in human leukemia U937 cells through activation of p38 MAPK and modulation of Bcl-2 family.
abstract: The present study investigated possible mechanisms on the apoptosis induction of human leukemic cells by fucoidan, a sulfated polysaccharide found in marine algae. Fucoidan treatment of cells resulted in inhibition of growth and induction of apoptosis, as measured by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyl-tetrazolium (MTT) assay, fluorescence microscopy, DNA fragmentation, and flow cytometry analysis. The increase in apoptosis was associated with the proteolytic activation of caspases, Bid cleavage, insertion of pro-apoptotic Bax into the mitochondria, release of cytochrome c from mitochondria to cytosol, and loss of mitochondria membrane potential (MMP) in U937 cells. However, apoptosis induced by fucoidan was attenuated by caspase inhibitors, indicating that fucoidan-induced apoptosis was dependent on the activation of caspases. Furthermore, fucoidan treatment effectively activated the p38 mitogen-activated protein kinase (MAPK) and p38 MAPK inhibitor, SB203580, and significantly reduced fucoidan-induced apoptosis through inhibition of Bax translocation and caspases activation, suggesting that the activation of p38 MAPK may play a key role in fucoidan-induced apoptosis. In addition, the authors found fucoidan-induced significantly attenuated in Bcl-2 overexpressing U937 cells, and pretreatment with fucoidan and HA 14-1, a small-molecule Bcl-2 inhibitor, markedly increased fucoidan-mediated apoptosis in Bcl-2 overexpressing U937 cells. Our findings imply that we may attribute some of the biological functions of p38 MAPK and Bcl-2 to their ability to inhibit fucoidan-induced apoptosis.
authors.affiliation: Department of Pharmacy, Pusan National University, Busan 609-735, Korea. phsvic@naver.com
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Park
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Hwang
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Hee-Jae
authors.initials: HJ
authors.lastname: Cha
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D020298:U937 Cells; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D011134:Polysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C007789:fucoidan; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases