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Mar. Drugs 2013, 11(7), 2347-2364; doi:10.3390/md11072347

Induction of Apoptosis by Fucoidan in Human Leukemia U937 Cells through Activation of p38 MAPK and Modulation of Bcl-2 Family

7,*  and 3,8,*
1 Department of Pharmacy, Pusan National University, Busan 609-735, Korea 2 Department of Food and Nutrition, Dongeui University, Busan 614-714, Korea 3 Anti-Aging Research Center & Blue-Bio Industry Regional Innovation Center, Dongeui University, Busan 614-714, Korea 4 Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Korea 5 Departments of Parasitology and Genetics, Kosin University College of Medicine, Busan 602-702, Korea 6 Department of Urology, Chungbuk National University College of Medicine, Cheongju 361-763, Korea 7 Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714, Korea 8 Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Korea
* Authors to whom correspondence should be addressed.
Received: 26 April 2013 / Revised: 30 May 2013 / Accepted: 13 June 2013 / Published: 4 July 2013
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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.
Keywords: fucoidan; leukemic cells; apoptosis; p38 MAPK; Bcl-2 fucoidan; leukemic cells; apoptosis; p38 MAPK; Bcl-2
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Park, H.S.; Hwang, H.J.; Kim, G.-Y.; Cha, H.-J.; Kim, W.-J.; Kim, N.D.; Yoo, Y.H.; Choi, Y.H. Induction of Apoptosis by Fucoidan in Human Leukemia U937 Cells through Activation of p38 MAPK and Modulation of Bcl-2 Family. Mar. Drugs 2013, 11, 2347-2364.

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