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Î±- and Î³-Mangostin inhibit the proliferation of colon cancer cells via Î²-catenin gene regulation in Wnt/cGMP signalling
- Yoo, Ji-Hye, Kang, Kyungsu, Jho, Eun Hye, Chin, Young-Won, Kim, Jinwoong, Nho, Chu Won
- Food chemistry 2011 v.129 no.4 pp. 1559-1566
- carcinogenesis, colorectal neoplasms, cyclic GMP, genes, phosphorylation, protein synthesis, xanthones
- Aberrant activation of Wnt/Î²-catenin signalling via genetic errors within Î²-catenin or APC has a crucial role in carcinogenesis. Here, we studied two xanthones, Î±- and Î³-mangostin, as inhibitors of Wnt/Î²-catenin signalling. The mangostins inhibited TCF/Î²-catenin transcriptional activity. The mangostins also inhibited protein expression of Î²-catenin in colon cancer cells, but the inhibition was independent of the phosphorylation and degradation of Î²-catenin. Instead, the mangostins increased the levels of cGMP and cGMP-dependent kinase, indicating that the inhibition of Î²-catenin resulted from Î²-catenin gene regulation. Our results indicate that mangostins could be potential candidates for preventing colon cancer through a novel mechanism of inhibiting Wnt/Î²-catenin signalling.