Structural characteization and anti-colorectal cancer activity of a fucogalactan purified from Ganoderma tsugae

Ganoderma tsugae, a traditional medicinal mushroom, exhibits anti-tumor properties; however, the effects of its polysaccharide on anti-colorectal cancer remain undetermined. Herein, a fucogalactan of Ganoderma tsugae (GTP-a2) was isolated and purified from its fruiting body. The molecular weight of GTP-a2 is 7.056 kDa, consisting of →6)-α-D-Galp-(1→ backbone with branches of α-L-Fucp-(1→, which is attached at C2. Subsequently, the anti-colorectal cancer activity and potential mechanism of GTP-a2 were investigated in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated colorectal cancer (CAC) mice. GTP-a2 reduced colorectal tumor numbers and suppressed tumor development. Metabolite analysis of the colon revealed that GTP-a2 altered cancer-related metabolites, notably increasing ophiobolin A level. Combined with proteomics and biochemical detection data revealed that GTP-a2 regulated the levels of Aldh1a3 through the mammalian target of rapamycin (mTOR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in vivo and in vitro. Additionally, GTP-a2 regulated immune function by inhibiting macrophage polarization to M1-like phenotype. These results suggest the potential application of GTP-a2 as a therapeutic agent for CAC.