Polysaccharide from Ganoderma atrum evokes antitumor activity via Toll-like receptor 4-mediated NF-κB and mitogen-activated protein kinase signaling pathways

Abstract

Ganoderma atrum has been used as a traditional Chinese medicine for centuries. In this study, the antitumor activity of a novel G. atrum polysaccharide (PSG-1) was investigated in vitro and in vivo using S180 tumor-bearing mice. The results showed that PSG-1 significantly inhibited the proliferation of S180 via the activation of macrophages in a dose-dependent manner. PSG-1-primed macrophages exhibited a higher tumoricidal activity than untreated macrophages. Administration of PSG-1 significantly inhibited the growth of transplantable sarcoma S180-bearing mice and increased macrophage phagocytosis and the levels of cytokines and nitride oxide. Expression of Toll-like receptor (TLR) 4 in the membrane was markedly increased in PSG-1-treated groups, suggesting that it may be a possible receptor for PSG-1. PSG-1 also promoted the translocation of the p65 subunit of NF-κB from cytosol to nucleus and the degradation of IκBα. Moreover, the phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2, and c-Jun N-terminal kinase in macrophages was improved by PSG-1 in a dose-dependent manner. Therefore, it is suggested that PSG-1 may elicit its antitumor effect by improving immune system functions through TLR4-mediated NF-κB and MAPK signaling pathways.