Antitumor and immunomodulatory activity of a water-soluble polysaccharide from Grifola frondosa.

Grifola frondosa has long been known and respected as a medically important fungus. This study investigated the characterization, antitumor and immunomodulatory activity of a polysaccharide named GP11 purified from G. frondosa. The results revealed that GP11 was composed of → 1)-D-Manp-(6 →,→ 1)-D-Glcp-(4 →,→ 1)-D-Galp-(6 → and → 2,3,6)-D-Glcp-(1 →, with branches attached at O-2,3 of 1,2,3,6-linked Glcp residues and terminal T-Glcp. GP11 exhibited indirect cytotoxic activity against HepG-2 cells in vitro, and it significantly inhibited the growth of Heps cells in vivo. GP11 increased the relative thymus and spleen weights as well as serum tumor necrosis factor-alpha and interleukin-2 levels. GP11 stimulated tumoricidal activity and the production of nitric oxide (NO), TNF-α and interleukin-1β, and it also stimulated the protein expression of iNOS and mRNA expression of iNOS and TNF-α. TLR-4 is a potential receptor for GP11-mediated macrophage activation. The results suggested that the antitumor activity of GP11 may be due to the improvement of immune functions through the TLR-4-mediated up-regulation of NO and TNF-α.