alpha- and gamma-Mangostin inhibit the proliferation of colon cancer cells via beta-catenin gene regulation in Wnt/cGMP signalling

Abstract

Aberrant activation of Wnt/beta-catenin signalling via genetic errors within beta-catenin or APC has a crucial role in carcinogenesis. Here, we studied two xanthones, alpha- and gamma-mangostin, as inhibitors of Wnt/beta-catenin signalling. The mangostins inhibited TCF/beta-catenin transcriptional activity. The mangostins also inhibited protein expression of beta-catenin in colon cancer cells, but the inhibition was independent of the phosphorylation and degradation of beta-catenin. Instead, the mangostins increased the levels of cGMP and cGMP-dependent kinase, indicating that the inhibition of beta-catenin resulted from beta-catenin gene regulation. Our results indicate that mangostins could be potential candidates for preventing colon cancer through a novel mechanism of inhibiting Wnt/beta-catenin signalling. (C) 2011 Elsevier Ltd. All rights reserved.