Title : Anticancer properties of fucoidan and its potential molecular targets

Fucoidan is a sulphated polysaccharide derived from the cell walls of brown seaweeds that has been widely studied for its diverse biological activities, including anticancer effects. Previous studies suggest that variations in monosaccharide composition and sulphation patterns influence the biological activity of fucoidan through interactions with multiple cellular targets and signalling pathways. While molecular regulators and signalling pathways such as Bax, Bcl-2, and Wnt/β-catenin are implicated in fucoidan-mediated apoptosis, proliferation, and cell cycle regulation, our understanding of the structural features of fucoidan and its precise molecular targets remains limited. Therefore, this study aimed to characterise fucoidan extracted from Turbinaria decurrens and evaluate its anticancer activity against colorectal cancer (CRC) cells.

Fucoidan was extracted from T. decurrens, purified using ion-exchange chromatography, and characterised using techniques including nuclear magnetic resonance (NMR) spectroscopy and high-performance anion-exchange chromatography. The anticancer activity of fucoidan was examined in SW480, HT29, and HCT116 colorectal cancer cells by evaluating cytotoxicity, migration, colony formation, cell cycle distribution, and apoptotic induction. Finally, multi-omics approaches, including proteomic and metabolomic analyses, were applied to investigate the molecular targets and mechanisms underlying fucoidan activity.

The fucoidan selected for anticancer testing had a molecular weight of 74.5 kDa, sulphate content of 33.4 %, monosaccharides dominated by fucose and galactose, with α-L-(1 → 3) Fucp and α-(1 → 4)-Fucp linkages identified as major structural features. Fucoidan exhibited significant cytotoxicity in all CRC cell lines and inhibited cell migration at 250 µg/mL. At 500 µg/mL, fucoidan induced G0/G1 phase arrest in HT29 and HCT116 cells, but not in SW480 cells. Ongoing multi-omics integration aims to identify molecular targets underlying fucoidan-mediated anticancer activity.

Keywords: Fucoidan, structural characteristics; anticancer properties; molecular targets; multi-omics

Emmanuel Ofosu Mensah is a PhD candidate at Macquarie University, Sydney, Australia, researching the therapeutic potential of seaweed-derived bioactive compounds. He holds a Bachelor's degree in Biochemistry and a Master's degree in Biotechnology. His undergraduate research focused on the antimicrobial properties of plant-derived natural products, while his master's research in Russia investigated nanoparticle-based delivery systems for bioactive compounds and therapeutic agents. His current research integrates natural product chemistry, molecular biology, and multi-omics approaches to investigate the anti-inflammatory and anticancer mechanisms of fucoidan, with the aim of advancing its development as a marine-derived nutraceutical and therapeutic candidate.