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Open AccessCommunication
Mar. Drugs 2019, 17(1), 54; https://doi.org/10.3390/md17010054

Pathway Analysis of Fucoidan Activity Using a Yeast Gene Deletion Library Screen

1
School of Medicine, University of Tasmania; Hobart TAS 7001, Australia
2
Marinova Pty Ltd., Cambridge TAS 7170, Australia
3
School of Health Sciences, University of Tasmania, Newnham TAS 7248, Australia
*
Authors to whom correspondence should be addressed.
Received: 14 December 2018 / Revised: 3 January 2019 / Accepted: 8 January 2019 / Published: 14 January 2019
(This article belongs to the Collection Marine Polysaccharides)
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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. View Full-Text
Keywords: fucoidan; Undaria pinnatifida; yeast gene deletion library; HCT-116 fucoidan; Undaria pinnatifida; yeast gene deletion library; HCT-116
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Corban, M.; Ambrose, M.; Pagnon, J.; Stringer, D.; Karpiniec, S.; Park, A.; Eri, R.; Fitton, J.H.; Gueven, N. Pathway Analysis of Fucoidan Activity Using a Yeast Gene Deletion Library Screen. Mar. Drugs 2019, 17, 54.

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