Bufalin inhibits gastric cancer invasion and metastasis by down-regulating Wnt/ASCL2 expression.

Achaete-scute-like 2 (ASCL2) is a transcription factor containing a basic helix-loop-helix (bHLH) domain and is a downstream target of Wnt signaling in intestinal stem cells. Bufalin is the primary active ingredient in Chan Su, a traditional Chinese medicine obtained from the skin and parotid venom glands of toads. The purpose of this study was to research the anti-invasion and anti-metastasis activity of bufalin in gastric cancer and to identify the potential mechanism. Bufalin inhibited gastric cancer cell invasion and metastasis, suppressed cancer cell colony formation, and inhibited the growth of subcutaneous xenografted tumors in nude mice. Furthermore, bufalin inhibited ASCL2 expression and down-regulated the expression of invasion-related genes such as MMP2, MMP9, and vimentin, thereby suppressing epithelial-mesenchymal transition (EMT) in gastric cancer. A Wnt signaling inhibitor (XAV939) down-regulated invasion and the expression of ASCL2, ß-catenin, and vimentin but up-regulated E-cadherin expression. In nude mice, bufalin inhibited the tumorigenic behavior of gastric cancer cells, induced cancer cell apoptosis, and regulated invasion-related gene expression. Together, our results suggest that bufalin arrests invasion and metastasis and that its mechanism of action may involve down-regulating Wnt/ASCL2 expression.

Molecular mechanisms underlying the antimetastatic activity of bufalin.

Bufalin is a monomer compound extract from Chansu, which is a traditional Chinese medicine obtained from the skin and parotid venom glands of toads, such as Bufo bufo gargarizans Cantor and Bufo melanostictus Schneider. Chansu had been used in traditional Chinese medicine for >1,000 years due to its cardiac, anti-inflammatory and anticancer properties. Previous studies identified bufalin as the main anticancer compound of Chansu, and recent evidence has corroborated its anticancer properties. Bufalin inhibits cancer cell proliferation, induces cell cycle arrest, induces cancer cell apoptosis, inhibits neovascularization, induces cell differentiation, inhibits cancer metastasis and invasion, and enhances chemotherapeutic drug sensitivity. However, the function and mechanism of bufalin in metastatic cancer cells have not yet been expounded. The aim of the present review was to discuss the recent progress and prospects of bufalin in the prevention of cancer metastasis, particularly in inhibiting epithelial-to-mesenchymal transition.