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Pathway analysis of fucoidan activity using a yeast gene deletion library screen

Citation

Corban, M and Ambrose, M and Pagnon, J and Stringer, D and Karpiniec, S and Park, A and Eri, R and Fitton, JH and Gueven, N, Pathway analysis of fucoidan activity using a yeast gene deletion library screen, Marine drugs, 17, (1) pp. 1-15. ISSN 1660-3397 (2019) [Refereed Article]


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Copyright 2019 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.3390/md17010054

Abstract

Fucoidan, the sulfated fucose-rich polysaccharide derived from brown macroalgae, was reported to display some anti-cancer effects in in vitro and in vivo models that included apoptosis and cell cycle arrest. The proposed mechanisms of action involve enhanced immune surveillance and direct pro-apoptotic effects via the activation of cell signaling pathways that remain largely uncharacterized. This study aimed to identify cellular pathways influenced by fucoidan using an unbiased genetic approach to generate additional insights into the anti-cancer effects of fucoidan. Drug⁻gene interactions of Undaria pinnatifida fucoidan were assessed by a systematic screen of the entire set of 4,733 halpoid Saccharomyces cerevsiae gene deletion strains. Some of the findings were confirmed using cell cycle analysis and DNA damage detection in non-immortalized human dermal fibroblasts and colon cancer cells. The yeast deletion library screen and subsequent pathway and interactome analysis identified global effects of fucoidan on a wide range of eukaryotic cellular processes, including RNA metabolism, protein synthesis, sorting, targeting and transport, carbohydrate metabolism, mitochondrial maintenance, cell cycle regulation, and DNA damage repair-related pathways. Fucoidan also reduced clonogenic survival, induced DNA damage and G1-arrest in colon cancer cells, while these effects were not observed in non-immortalized human fibroblasts. Our results demonstrate global effects of fucoidan in diverse cellular processes in eukaryotic cells and further our understanding about the inhibitory effect of Undaria pinnatifida fucoidan on the growth of human cancer cells.

Item Details

Item Type:Refereed Article
Keywords:fucoidan, pharmacogenomics
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Pharmaceutical Sciences
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
UTAS Author:Corban, M (Ms Monika Corban)
UTAS Author:Ambrose, M (Dr Mark Ambrose)
UTAS Author:Pagnon, J (Ms Joanne Pagnon)
UTAS Author:Eri, R (Associate Professor Raj Eri)
UTAS Author:Fitton, JH (Dr Helen Fitton)
UTAS Author:Gueven, N (Dr Nuri Guven)
ID Code:130391
Year Published:2019
Deposited By:Pharmacy
Deposited On:2019-01-23
Last Modified:2019-07-23
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