Fucoidan from Laminaria cichorioides inhibits AP‐1 transactivation and cell transformation in the mouse epidermal JB6 cells

Abstract

Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, has anticoagulant and antithrombotic activities. Unlike heparine, fucoidan is known to exhibit anticarcinogenic activities. However, the underlying molecular mechanisms of the chemopreventive activities of fucoidan are not understood. Here we report that fucoidan from Laminaria cichorioides inhibited the epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic cell transformation, but had less cytotoxic effects on JB6 mouse epidermal cells. The EGF-induced phosphorylation of extracellular signal-regulated kinases 1/2 and c-Jun N-terminal kinases, and c-Jun was inhibited by fucoidan, resulting from the inhibition of phosphorylation of epidermal growth factor receptor (EGFR). Fucoidan dose-dependently attenuated the c-fos or c-jun transcriptional activity, and thereby inhibited the associated activator protein-1 (AP-1) transactivation activity. In vitro binding assay revealed that fucoidan directly interacted with EGF, suggested that antitumor promoting effect of fucoidan might be due to preventing the binding of EGF to its cell surface receptor (EGFR). These findings are the first to reveal a molecular basis for the anticarcinogenic action of fucoidan and may partially account for the reported chemopreventive effects of brown seaweeds.

Structural Characteristics and Biological Activity of Fucoidans from the Brown Algae Alaria sp. and Saccharina japonica of Different Reproductive Status

“…and S. japonica at different reproductive stages against normal mouse epidermal (JB6 Cl41), human breast cancer (T-47D), and melanoma (RPMI-7951) cell lines was tested (Fig. Similar results were obtained by Lee et al [32] [33], who showed that purified fucoidans isolated from Laminaria cichorioides and L. gurjanovae were nontoxic to JB6 mouse epidermal cells. The cells were incubated for 24 h with different concentrations of fucoidans (100, 200, 400, and 800 mg/ ml) isolated from vegetative (Al sp-sF and Sj-sF2) and reproductive tissues (Al sp-fF and Sj-fF2) of the brown algae.…”

Fucoidans from Brown Seaweeds Sargassum hornery, Eclonia cava, Costaria costata: Structural Characteristics and Anticancer Activity

“…The amount of sulfate groups has been reported to play role for anticoagulant activity of fucoidans. There are very few reports [14][15][16][17]4] in the literature on the relationship between chemical properties and anticancer activity of different fucoidans. In our case, we did not find a correlation between amount of sulfate groups and anticancer activity, as fucoidan ShF2 does not have sulfate groups, but its anticancer activity is the same as for fucoidan ShF3 with 16.9% of sulfate.…”

Anticancer and Cancer Preventive Properties of Marine Polysaccharides: Some Results and Prospects

“…Actually, in experiments with neoplastic transformation of JB6 mouse epidermal cells induced by EGF or 12- O -tetradecanoylphorbol-13 acetate, a Russian-Korean group of scientists reported that inhibition of EGFR phosphorylation was followed by inhibition of the activities of some extracellular signal regulated kinases that resulted in the inhibition of AP-1 nuclear factor transactivation [66,67]. …”