Cryptolepine Suppresses Colorectal Cancer Cell Proliferation, Stemness, and Metastatic Processes by Inhibiting...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Colorectal cancer (CRC) is a leading cause of cancer death globally.
• Over 90% of CRC cases involve a deregulated Wingless Integrated Type-1 (WNT)/β-catenin signaling pathway.
• This pathway drives CRC cell proliferation, stemness, and metastasis, making it a therapeutic target.

Purpose of the Study:

• To investigate the effect of cryptolepine, a plant-derived compound, on the WNT/β-catenin pathway in colorectal cancer (CRC).
• To evaluate cryptolepine's potential as a WNT pathway inhibitor for CRC treatment.

Main Methods:

• Treated COLO205 and DLD1 CRC cell lines with cryptolepine or XAV 939, with or without WNT3a activation.
• Assessed cell viability using a tetrazolium-based assay.
• Analyzed gene expression (β-catenin, c-MYC, WISP1, OCT4, CD133, SNAI1, TWIST1, MMP2, MMP9) via RT-qPCR.
• Evaluated stemness (colony formation) and migration (wound healing assay).

Main Results:

• Cryptolepine significantly reduced CRC cell viability, outperforming XAV 939.
• Cryptolepine reversed WNT3a-induced expression of key WNT/β-catenin pathway genes (β-catenin, c-MYC, WISP1).
• Cryptolepine suppressed CRC stemness (OCT4, CD133, colony formation) and metastasis (SNAI1, TWIST1, MMP2, MMP9, cell migration).

Conclusions:

• Cryptolepine inhibits WNT3a-mediated activation of the WNT/β-catenin signaling pathway in CRC cells.
• Cryptolepine effectively suppresses CRC cell proliferation, stemness, and metastatic properties.
• Cryptolepine demonstrates potential as a novel therapeutic agent for colorectal cancer.