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Raddeanin A Inhibits Colorectal Cancer Growth and Ameliorates Oxaliplatin Resistance Through the WNT/β-Catenin Signaling Pathway

Title: Raddeanin A Inhibits Colorectal Cancer Growth and Ameliorates Oxaliplatin Resistance Through the WNT/β-Catenin Signaling Pathway
Authors: Chen, Junguo; Zhang, Yanhong; Chen, Xijie; Luo, Dandong; Liu, Danlin; Yu, Zhaoliang; Lin, Yanyun; He, Xiaosheng; Huang, Juanni; Lian, Lei
Source: Cancer Biotherapy and Radiopharmaceuticals ; volume 40, issue 1, page 41-53 ; ISSN 1084-9785 1557-8852
Publisher Information: SAGE Publications
Publication Year: 2025
Description: Background: Chemotherapy based on oxaliplatin (OXA) is the first-line treatment for advanced colorectal cancer (CRC), and acquired resistance to OXA is the main reason for clinical treatment failure in CRC. Methods: To search for compounds that can reverse OXA resistance, we screened a small molecule inhibitor drug library and identified a drug, Raddeanin A (RA), that enhanced the anticancer effect of OXA. Using human CRC cell lines, CRC organoid models, and in vivo subcutaneous tumorigenic studies, we determined that RA inhibits the proliferation of CRC cells by promoting apoptosis and inducing cell cycle arrest. Results: We constructed OXA-resistant CRC cell lines and demonstrated that RA enhances the sensitivity of these cells to OXA. Further experiments showed that the mechanism by which RA enhanced the anticancer effects of OXA in CRC was by inhibiting the activation of the WNT/β-catenin signaling pathway. Conclusions: Because RA has been shown to be biocompatible in animal models, there is a possibility that RA could be developed as a sensitizer for resistant cancer cells or as a novel lead compound to enhance the therapeutic efficacy of OXA in resistant CRCs.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1089/cbr.2024.0061
Availability: https://doi.org/10.1089/cbr.2024.0061; https://journals.sagepub.com/doi/full-xml/10.1089/cbr.2024.0061; https://journals.sagepub.com/doi/pdf/10.1089/cbr.2024.0061
Rights: https://creativecommons.org/licenses/by/4.0/ ; https://journals.sagepub.com/page/policies/text-and-data-mining-license
Accession Number: edsbas.A2EEA4C9
Database: BASE