Antitumor Activity of Rutaecarpine in Human Colorectal Cancer Cells by Suppression of Wnt/?-Catenin Signaling

Alkaloids derived from natural products have been traditionally used to treat various diseases, including cancers. Rutaecarpine (1), a beta-carboline-type alkaloid obtained from Evodia rutaecarpa, has been previously reported as an anti-inflammatory agent. Nonetheless, its anticancer activity and the underlying molecular mechanisms remain to be explored. In the procurement of Wnt/beta-catenin inhibitors from natural alkaloids, 1 was found to exhibit activity against the Wnt/beta-catenin-response reporter gene. Since the abnormal activation of Wnt/beta-catenin signaling is highly involved in colon carcinogenesis, the antitumor activity and molecular mechanisms of 1 were investigated in colorectal cancer (CRC) cells. The antiproliferative activity of 1 was associated with the suppression of the Wnt/beta-catenin-mediated signaling pathway and its target gene expression in human CRC cells. 1 also induced G(0)/G(1) cell cycle arrest and apoptotic cell death, and the antimigration and anti-invasion potential of 1 was confirmed through epithelial-mesenchymal transition biomarker inhibition by the regulation of Wnt signaling. The antitumor activity of 1 was supported in an Ls174T-implanted xenograft mouse model via Wnt target gene regulation. Overall, these findings suggest that targeting the Wnt/beta-catenin signaling pathway by 1 is a promising therapeutic option for the treatment of human CRC harboring beta-catenin mutation.

Automated summary

Rutaecarpine (1), a natural alkaloid derived from Evodia rutaecarpa, exhibits anticancer activity by targeting the abnormal activation of Wnt/β-catenin signaling pathway in colorectal cancer cells. It suppresses the proliferation of cancer cells, induces cell cycle arrest and apoptotic cell death, and inhibits migration and invasion potential through the regulation of Wnt signaling. The findings suggest that 1 could be a promising therapeutic option for the treatment of human colorectal cancer harboring β-catenin mutation.