α- and γ-Mangostin inhibit the proliferation of colon cancer cells via β-catenin gene regulation in Wnt/cGMP signalling

Aberrant activation of Wnt/β-catenin signalling via genetic errors within β-catenin or APC has a crucial role in carcinogenesis. Here, we studied two xanthones, α- and γ-mangostin, as inhibitors of Wnt/β-catenin signalling. The mangostins inhibited TCF/β-catenin transcriptional activity. The mangostins also inhibited protein expression of β-catenin in colon cancer cells, but the inhibition was independent of the phosphorylation and degradation of β-catenin. Instead, the mangostins increased the levels of cGMP and cGMP-dependent kinase, indicating that the inhibition of β-catenin resulted from β-catenin gene regulation. Our results indicate that mangostins could be potential candidates for preventing colon cancer through a novel mechanism of inhibiting Wnt/β-catenin signalling.