Cryptolepine Suppresses Colorectal Cancer Cell Proliferation, Stemness, and Metastatic Processes by Inhibiting WNT/β-Catenin Signaling

Colorectal cancer (CRC) is the third most frequent and second leading cause of cancer-related deaths globally. Evidence shows that over 90% CRC cases are initiated by a deregulated Wingless Integrated Type-1 (WNT)/β-catenin signaling pathway. The WNT/β-catenin pathway also promotes cell proliferation, stemness, metastasis. Therefore, modulators may serve as promising regimens for CRC. This study investigated effect cryptolepine—a plant-derived compound—on in Two lines, COLO205 DLD1, were treated with cryptolepine or XAV 939 (a WNT inhibitor) presence absence WNT3a activator). Using tetrazolium-based assay, was found to reduce viability dose- time-dependent manner more potent inhibitor than 939. RT-qPCR analyses showed reverses WNT3a-induced expression β-catenin, c-MYC, WISP1, suggesting inhibits WNT3a-mediated activation signaling. Cryptolepine repressed OCT4 CD133 suppressed colony formation cells, indicating stemness cells. Additionally, inhibited epithelial-to-mesenchymal transition reducing SNAI1 TWIST1 genes. In wound healing suppress migration under unstimulated WNT3a-stimulated conditions. Moreover, downregulated MMP2 MMP9 genes, which involved invasion. Altogether, suppresses metastatic properties inhibiting These findings provide rationale considering potential