Potent activation of tumor necrosis factor-α production by a polysaccharide found in a marine brown alga Chordaria flagelliformis

In a search for new antitumor drugs, we collected 334 species of marine algae from the Japanese coastline and screened these for tumor necrosis factor-alpha (TNF-α) production-promoting activity in an in vitro assay with the mouse macrophage-derived cell line RAW264.7. A phosphate-buffered saline extract from the marine brown alga Chordaria flagelliformis was found to strongly promote TNF-α activity. Further purification of this alga by precipitation with ethanol and two-step chromatography yielded an approximately 3,000-kDa polysaccharide as the active substance, which we designated MC25. MC25 exhibited TNF-α production-promoting activity in RAW264.7 cells in a dose-dependent manner, and we established its temperature and pH stabilities and non-cytotoxic character. Its molecular structure is similar to that of a fucoidan in terms of composition, including glucose, fucose, xylose, and uronic acid. The molecule hydrolyzed to a size of 180–370 kDa still retained strong TNF-α production-promoting activity, suggesting that MC25 might be a promising candidate in the development of novel antitumor agents.