Targeting the β-Catenin/Wnt Signaling for Cancer Therapy

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (25 March 2024) | Viewed by 1842

Special Issue Editor

Institut de Recherche en Cancérologie de Montpellier (IRCM), University of Montpellier, ICM, INSERM U1194, Montpellier, France
Interests: protein kinase Cα; tumor suppressor; nanovector; SOX9 transcription factor; colorectal cancer; wnt/beta-catenin signaling; therapeutic peptides
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Wnt signalling pathway plays a critical role in cell proliferation, migration, polarity and self-renewal at all stages of life, from early development during embryonic stages to adult tissue homeostasis. Consequently, aberrant and disarrayed Wnt signalling is observed in the majority of cancers, and therefore, Wnt signalling components are attractive therapeutic targets when considering the treatment of various cancers. Mutation-induced activation of the Wnt/β-catenin pathway has also been identified as a frequent driver of human cancers, thus opening up exciting new avenues of research for cancer treatment. Based on these observations, novel strategies have been proposed and new drugs have been developed to block the interaction of extracellular and intracellular deregulated molecules at the transcriptional as well as translational levels so that downstream activation of the target genes is prevented. Natural antagonists of the Wnt pathway, such as secreted frizzled-related proteins (SFRPs), Dkk, ligand–receptor complexes, etc., were also made use of to trigger apoptosis in cancer cells. Studies on repurposing existing drugs have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of developing colorectal cancer by lowering the levels of nuclear β-catenin and triggering its degradation. These recent developments in this field and the concomitant understanding of the Wnt/B-catenin signaling pathways have kindled new-found hope for cancer treatment. This Special Issue, entitled "Targeting β-catenin/Wnt Signalling for Cancer Therapy", aims to sum up and highlight the latest fundamental, clinical and conceptual developments in this field. We sincerely hope that it will provide an accessible reference for furthering research in cancer therapy.

Dr. Corinne Prévostel
Guest Editor

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Research

16 pages, 4678 KiB  
Article
Cryptolepine Suppresses Colorectal Cancer Cell Proliferation, Stemness, and Metastatic Processes by Inhibiting WNT/β-Catenin Signaling
by Jude Tetteh Quarshie, Kwadwo Fosu, Nicholas Awuku Offei, Augustine Kojo Sobo, Osbourne Quaye and Anastasia Rosebud Aikins
Pharmaceuticals 2023, 16(7), 1026; https://doi.org/10.3390/ph16071026 - 19 Jul 2023
Viewed by 1480
Abstract
Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer-related deaths globally. Evidence shows that over 90% of CRC cases are initiated by a deregulated Wingless Integrated Type-1 (WNT)/β-catenin signaling pathway. The WNT/β-catenin pathway also promotes CRC [...] Read more.
Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer-related deaths globally. Evidence shows that over 90% of CRC cases are initiated by a deregulated Wingless Integrated Type-1 (WNT)/β-catenin signaling pathway. The WNT/β-catenin pathway also promotes CRC cell proliferation, stemness, and metastasis. Therefore, modulators of the WNT/β-catenin pathway may serve as promising regimens for CRC. This study investigated the effect of cryptolepine—a plant-derived compound—on the WNT/β-catenin pathway in CRC. Two CRC cell lines, COLO205 and DLD1, were treated with cryptolepine or XAV 939 (a WNT inhibitor) in the presence or absence of WNT3a (a WNT activator). Using a tetrazolium-based assay, cryptolepine was found to reduce cell viability in a dose- and time-dependent manner and was a more potent inhibitor of viability than XAV 939. RT-qPCR analyses showed that cryptolepine reverses WNT3a-induced expression of β-catenin, c-MYC, and WISP1, suggesting that cryptolepine inhibits WNT3a-mediated activation of WNT/β-catenin signaling. Cryptolepine also repressed WNT3a-induced OCT4 and CD133 expression and suppressed colony formation of the cells, indicating that cryptolepine inhibits the stemness of CRC cells. Additionally, cryptolepine inhibited WNT3a-induced epithelial-to-mesenchymal transition by reducing the expression of SNAI1 and TWIST1 genes. In a wound healing assay, cryptolepine was found to suppress cell migration under unstimulated and WNT3a-stimulated conditions. Moreover, cryptolepine downregulated WNT3a-induced expression of MMP2 and MMP9 genes, which are involved in cancer cell invasion. Altogether, cryptolepine suppresses CRC cell proliferation, stemness, and metastatic properties by inhibiting WNT3a-mediated activation of the WNT/β-catenin signaling pathway. These findings provide a rationale for considering cryptolepine as a potential WNT inhibitor in CRC. Full article
(This article belongs to the Special Issue Targeting the β-Catenin/Wnt Signaling for Cancer Therapy)
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