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Fucoidan suppresses the growth of human acute promyelocytic leukemia cells in vitro and in vivo

Citation

Atashrazm, F and Lowenthal, RM and Woods, GM and Holloway, AF and Karpiniec, SS and Dickinson, JL, Fucoidan suppresses the growth of human acute promyelocytic leukemia cells in vitro and in vivo, Journal of Cellular Physiology, 231, (3) pp. 688-697. ISSN 0021-9541 (2015) [Refereed Article]


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DOI: doi:10.1002/jcp.25119

Abstract

Fucoidan, a natural component of seaweeds, is reported to have immunomodulatory and anti-tumor effects. The mechanisms underpinning these activities remain poorly understood. In this study, the cytotoxicity and anti-tumor activities of fucoidan were investigated in acute myeloid leukemia (AML) cells. The human AML cell lines NB4, KG1a, HL60 and K562 were treated with fucoidan and cell cycle, cell proliferation and expression of apoptotic pathways molecules were analyzed. Fucoidan suppressed the proliferation and induced apoptosis through the intrinsic and extrinsic pathways in the acute promyelocytic leukemia (APL) cell lines NB4 and HL60, but not in KG1a and K562 cells. In NB4 cells, apoptosis was caspase-dependent as it was significantly attenuated by pre-treatment with a pan-caspase inhibitor. P21/WAF1/CIP1 was significantly up-regulated leading to cell cycle arrest. Fucoidan decreased the activation of ERK1/2 and down-regulated the activation of AKT through hypo-phosphorylation of Thr(308) residue but not Ser(473). In vivo, a xenograft model using the NB4 cells was employed. Mice were fed with fucoidan and tumor growth was measured following inoculation with NB4 cells. Subsequently, splenic natural killer (NK) cell cytotoxic activity was also examined. Oral doses of fucoidan significantly delayed tumor growth in the xenograft model and increased cytolytic activity of NK cells. Taken together, these data suggest that the selective inhibitory effect of fucoidan on APL cells and its protective effect against APL development in mice warrant further investigation of fucoidan as a useful agent in treatment of certain types of leukemia.

Item Details

Item Type:Refereed Article
Keywords:fucoidan, apoptosis, leukemia, immunomodulation
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Cellular Immunology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
Author:Atashrazm, F (Miss Farzaneh Atashrazm)
Author:Lowenthal, RM (Professor Ray Lowenthal)
Author:Woods, GM (Professor Gregory Woods)
Author:Holloway, AF (Dr Adele Holloway)
Author:Dickinson, JL (Associate Professor Joanne Dickinson)
ID Code:102306
Year Published:2015
Web of Science® Times Cited:5
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-08-12
Last Modified:2017-11-07
Downloads:2 View Download Statistics

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