Fucoidan Treatment Leads to Attenuated Growth Factor Signaling and Reduced Proliferation in Neuroblastoma Cells.

BACKGROUND/AIM: Brown algae-derived sulfated polysaccharides, termed as fucoidans, are pharmacologically active substances with pleiotropic anticancer properties, but without known toxicity. In neuroblastoma, an aggressive malignancy with a heterogeneous biological basis, multimodal therapeutic approaches are mandatory for high-risk patients, but these are associated with a problematic safety profile. The present study aimed to examine fucoidan-mediated effects in human neuroblastoma cells to assess their putative tumor-suppressive potential.

MATERIALS AND METHODS

In Kelly or SH-SY5Y cells, viability was quantified using cell fitness assays. Expression was analyzed using quantitative PCR and the regulation or phosphorylation of proteins using enzyme-linked immunoabsorbent assays (ELISA) or Western blots.

RESULTS

In Kelly and SH-SY5Y cells, treatment with fucoidans from (F.v.) or (S.l.) for 3 days did not induce cell death, but significantly reduced proliferation (<0.001), which was associated with attenuated signaling of hepatocyte growth factor (HGF), insulin-like growth factor 2 (IGF2) and vascular endothelial growth factor (VEGF). Despite cell type- and fucoidan-specific differences, co-administration of the fucoidans from F.v. or S.l. and specific receptor inhibitors of HGF (tepotinib), IGF2 (linsitinib) or VEGF (cediranib), distinctly reduced cell viability compared to inhibitor treatment alone in both cell lines (<0.001). Interestingly, the fucoidan from S.l. also enhanced the antitumor effect of the endothelial growth factor (EGF) receptor inhibitor erlotinib in Kelly and SH-SY5Y cells, although endogenous EGF was not detectable.

CONCLUSION

Fucoidan treatment decreased proliferation in neuroblastoma cells by interfering with the signal transduction of HGF, IGF2, and VEGF, which substantially increased cellular susceptibility to specific growth factor receptor inhibitors.