Fucoidan exerts anti-cancer activity in a 3D prostate spheroid cell culture model.
Jelena VideriD, Todd ShelperiD, Katherine Ting Wei LeeiD, J. Helen FittoniD, Nicholas Peter WestiD
Abstract
To investigate the effect of fucoidan on the viability, migration and mRNA/microRNA profiles of two prostate cancer cell lines in 3D culture (spheroids). Hormone resistant, PC-3, and hormone sensitive, LNCaP, spheroids were incubated in the presence of a proprietary fucoidan blend extract from Undaria pinnatifida and Fucus vesiculosus. Magnetic bioprinting was used to assess cells migration/metastatic potential in response to fucoidan exposure. Cellular viability was assessed using a cytotoxicity lactate dehydrogenase (LDH) assay. nCounter (Nanostring) assays were used for microRNA and mRNA profiling in control and treated cells. Fucoidan treated PC-3 spheroids clearly showed a dose dependent viability/migration response and changes in spheroid structural morphology. Fifty-seven genes were significantly differentially expressed between fucoidan treated and non-treated PC-3 spheroids. No miRNAs at an adjusted p-value were significantly differentially expressed in PC-3 spheroids with fucoidan co-culture. Thirty-two genes were significantly differentially expressed in the fucoidan treated to non-treated LNCaP spheroids and there was a significant 3.5-fold (pAdj=0.012) increase in hsa-miR-1246 in the fucoidan treated compared to non-treated LNCaP spheroids. Gene sets enriched in fucoidan treated PC-3 spheroids related to DNA repair processes, cellular development, cell cycle and inflammation. These findings provide further pre-clinical evidence for a role for fucoidan in targeting cancer related pathways in both hormone sensitive and hormone resistant prostate cancer.
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