Antitumor Activity of Rutaecarpine in Human Colorectal Cancer Cells by Suppression of Wnt/β-Catenin Signaling.
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| Abstract |
Alkaloids derived from natural products have been traditionally used to treat various diseases, including cancers. Rutaecarpine (1), a β-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/β-catenin inhibitors from natural alkaloids, 1 was found to exhibit activity against the Wnt/β-catenin-response reporter gene. Since the abnormal activation of Wnt/β-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/β-catenin-mediated signaling pathway and its target gene expression in human CRC cells. 1 also induced G0/G1 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/β-catenin signaling pathway by 1 is a promising therapeutic option for the treatment of human CRC harboring β-catenin mutation.
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| Authors | Woong Sub Byun, Eun Seo Bae, Won Kyung Kim, Sang Kook Lee |
| Journal | Journal of natural products (J Nat Prod) Vol. 85 Issue 5 Pg. 1407-1418 (05 27 2022) ISSN: 1520-6025 [Electronic] United States |
| PMID | 35544614 (Publication Type: Journal Article, Review, Research Support, Non-U.S. Gov't) |
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