Fucoidan inhibits epithelial-to-mesenchymal transition via regulation of the HIF-1α pathway in mammary cancer cells under hypoxia.

This study examined the effects of fucoidan on epithelial-to-mesenchymal transition (EMT) in a human triple-negative breast cancer (TNBC) cell line in a hypoxic microenvironment. Transwell and wound-healing assays were performed to analyze the invasion and migration of MDA-MB-231 human mammary cancer cells, respectively. The expression levels of EMT markers and hypoxia-inducible factor-1α (HIF-1α) were detected through western blotting. Under hypoxia, fucoidan treatment inhibited proliferation of breast cancer cells. Fucoidan also suppressed the invasion and migration of MDA-MB-231 cells. Western blotting revealed that fucoidan treatment significantly reduced the protein expression levels of HIF-1α and HIF-1 target genes. Furthermore, the nuclear translocation and activity of HIF-1α were reduced. Fucoidan treatment significantly downregulated the expression levels of mesenchymal markers (N-cadherin and vimentin), but upregulated the expression levels of the epithelial markers zonula occludens-1 and E-cadherin. In addition, overexpression of HIF1-α protected cells from fucoidan-mediated suppression of migration and invasion. These data suggested that fucoidan may inhibit EMT in human TNBC cells via downregulation of the HIF1-α signaling pathway.