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

Marine Drugs

Hyun Soo Park⁴  Hye Jin Hwang⁵  Gi-Young Kim¹  Hee-Jae Cha²  Wun-Jae Kim³  Nam Deuk Kim⁴  Young Hyun Yoo⁶ 

[1] Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Korea; E-Mail:;Departments of Parasitology and Genetics, Kosin University College of Medicine, Busan 602-702, Korea; E-Mail:;Department of Urology, Chungbuk National University College of Medicine, Cheongju 361-763, Korea; E-Mail:;Department of Pharmacy, Pusan National University, Busan 609-735, Korea; E-Mails:;Department of Food and Nutrition, Dongeui University, Busan 614-714, Korea; E-Mail:;Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714, Korea

关键词: fucoidan;    leukemic cells;    apoptosis;    p38 MAPK;    Bcl-2;   

DOI  :  10.3390/md11072347

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.