Dieckol or phlorofucofuroeckol extracted from Ecklonia cava suppresses lipopolysaccharide-mediated human breast cancer cell migration and invasion

The phlorotannin compounds, dieckol and phlorofucofuroeckol (PFF), extracted from Ecklonia cava, have been suggested to exhibit anti-inflammatory, anti-adipogenic or anti-tumorigenic activity. However, role of dieckol or PFF in LPS/TLR-4 signaling that regulates cancer development still remains to be determined. Here we report that dieckol or PFF blocked lipopolysaccharide (LPS)-induced migration and invasion of human breast cancer MCF-7 or MDA-MB-231 cells by about 50% (p < 0.0001) or 60% (p = 0.0001), respectively. Also, PFF as well as dieckol markedly attenuated both of LPS-induced Toll-like receptor4 (TLR-4) expression and NF-kappa B promoter-driven transcriptional activity, which are essential for the migration and invasion. Moreover, LPS induction of NF-kappa B-dependent gene, matrix metalloproteinase9 (MMP-9) was markedly decreased about 2.6 or 2.5 fold by dieckol and PFF, respectively. In addition, LPS-induced MMP-2 gene expression was reduced about 1.7 or 2.1 fold by dieckol and PFF, respectively. Significantly, each inhibitor of MMP-9 or NF-kappa B notably reduced invasion of MDA-MB-231 cells in response to LPS by about 70% (p = 0.0115) or 40% (p < 0.0001), respectively. Collectively, these findings demonstrate that both of dieckol and PFF functions as a critical inhibitor of LPS-induced breast cancer cell invasion through downregulation of TLR-4-NF-kappa B-MMP-9 signaling axis, suggesting a potential role of the phlorotannins in inflammation-mediated breast cancer development.