Curcumin suppresses colorectal cancer by inhibiting TRIM2 and mTOR signaling

Abstract

Curcumin, a natural polyphenol, exhibits potent anti-cancer activities, but its underlying molecular mechanisms in colorectal cancer (CRC) are not fully elucidated. Here, we investigated t whether curcumin suppresses CRC by targeting tripartite motif-containing protein 2 (TRIM2) and its downstream the Mammalian Target of Rapamycin (mTOR) signaling pathway. We initially performed a whole-genome expression profile chip to examine gene alterations following curcumin administration. Our results demonstrate that curcumin effectively decreased the expression of TRIM2 in CRC cells. Furthermore, PCR and immunohistochemical (IHC) staining of tumour samples confirmed the elevated expression of TRIM2 in CRC cells and CRC tumour samples. Additionally, we assessed the effect of TRIM2 knockdown on the proliferation of CRC cells and tumour growth using cell and animal experiments. mTOR pathway activity was interrogated using phospho‑kinase arrays and immunoblotting, with pharmacologic rescue by an mTOR activator. Our findings revealed that curcumin administration and TRIM2 knockdown effectively suppressed the migration and proliferation of CRC cells and mTOR activation partially reversed these effects, Mechanistically, TRIM2 depletion dampened mTOR signaling, reducing phosphorylation of AKT (Ser473), and S6K/4EBP1 without altering total protein levels. These findings indicate curcumin inhibits CRC onset and progression by downregulating TRIM2 and suppressing mTOR pathway activity, suggesting TRIM2 may serve as a potential prognostic marker in CRC.