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

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. © 2008 Wiley‐Liss, Inc.