Cardamonin Suppresses the Proliferation of Colon Cancer Cells by Promoting β-Catenin Degradation

Aberrant accumulation of intracellular beta-catenin and subsequent activation of beta-catenin response transcription (CRT) in intestinal epithelial cells is a frequent early event during the development of colon cancer. Here we show that cardamonin, a chalcone isolated from Aplinia katsumadai HAYATA, inhibited CRT in SW480 colon cancer cells that carry inactivating mutation in the adenomatous polyposis coli (APC) gene. Cardamonin also down-regulated intracellular beta-catenin levels in SW480 cells without affecting its mRNA levels. Interestingly, pharmacological inhibition of the proteasome prevented the cardamonin-induced down-regulation of beta-catenin. In addition, cardamonin suppressed the expression of cyclin D1 and c-myc, which are known beta-catenin/T cell factor (TCF)-dependent genes. Moreover, cardamonin inhibited the growth of various colon cancer cells and induced G2/M cell cycle arrest in SW480 colon cancer cells. These findings indicate that cardamonin is a potential chemotherapeutic agent against colon cancer.