ORIGINAL RESEARCH article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1566889
Curcumin Inhibits Colorectal Cancer Progression by Targeting PTBP1 and CDK2-Mediated Pathways
Provisionally accepted
- The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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Background: Colorectal cancer (CRC) remains a significant cause of cancer-related mortality worldwide. Curcumin, a natural polyphenol, has shown promise in targeting key cancer pathways, but its precise molecular mechanisms in CRC are not fully understood. This study investigates the anti-cancer mechanisms of curcumin on CRC progression, focusing on PTBP1 and CDK2 as critical regulators. Methods: The expression of PTBP1 was assessed in clinical CRC samples and curcumin-treated cells via PCR and Western blot. Functional assaysincluding CCK8, colony formation, flow cytometry, Transwell migration/invasion, and apoptosis/autophagy staining-were conducted to evaluate curcumin's effects. CDK2 was identified as a direct target using pull-down, kinase activity, and immunoprecipitation assays. CDK2 knockout models were used to validate curcumin's effects in vitro and in vivo. Results: Curcumin markedly downregulated PTBP1 expression, and suppressed CRC cell proliferation, migration, and invasion while promoting apoptosis and autophagy. Mechanistic analysis revealed direct inhibition of CDK2 by curcumin, disrupting the CDK2c-MYC -PTBP1 regulatory axis. CDK2 knockout mimicked curcumin's effects but reduced the cells' sensitivity to the treatment. In vivo, curcumin significantly inhibited tumor growth and activated autophagy-related pathways. Conclusions: This study uncovers a novel mechanism in which curcumin suppresses CRC progression by targeting the CDK2c-MYC -PTBP1 axis. These findings provide compelling evidence for curcumin's therapeutic potential and support further clinical investigation.
Keywords: Curcumin, colorectal cancer, PTBP1, CDK2, Autophagy The effects of curcumin on CRC cell viability, proliferation, Migration, invasion
Received: 26 Jan 2025; Accepted: 30 Apr 2025.
Copyright: © 2025 Zheng, Li, Wang, Su, Wang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Fujing Wang, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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