Abstract
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 assays-including 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 CDK2-c-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 CDK2-c-MYC-PTBP1 axis. These findings provide compelling evidence for curcumin's therapeutic potential and support further clinical investigation.