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Curcumin suppresses colorectal cancer by inhibiting TRIM2 and mTOR signaling

Hang Yu1, Haikuo Wu1, Qianhui Zhao1

  • 1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.

Translational Oncology
|September 14, 2025
PubMed

Insights

Curcumin, a natural compound, inhibits colorectal cancer (CRC) by reducing tripartite motif-containing protein 2 (TRIM2) and the mTOR pathway. This suggests TRIM2 as a potential prognostic marker for CRC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Natural Products Chemistry

Background:

  • Colorectal cancer (CRC) remains a significant health challenge globally.
  • The anti-cancer properties of curcumin, a natural polyphenol, are recognized, but its precise molecular targets in CRC require further investigation.
  • Understanding the molecular mechanisms of curcumin in CRC is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To investigate whether curcumin suppresses colorectal cancer (CRC) by targeting tripartite motif-containing protein 2 (TRIM2) and its downstream Mammalian Target of Rapamycin (mTOR) signaling pathway.
  • To elucidate the molecular mechanisms underlying curcumin's anti-cancer effects in CRC.
  • To evaluate the potential of TRIM2 as a prognostic marker in CRC.

Main Methods:

  • Whole-genome expression profile chip analysis to identify gene alterations after curcumin administration.
  • Quantitative PCR and immunohistochemical (IHC) staining to assess TRIM2 expression in CRC cells and tissues.
  • Cell and animal experiments to evaluate the impact of TRIM2 knockdown on CRC cell proliferation and tumor growth.
  • Phospho-kinase arrays and immunoblotting to interrogate mTOR pathway activity, with pharmacologic rescue using an mTOR activator.

Main Results:

  • Curcumin significantly decreased TRIM2 expression in CRC cells.
  • Elevated TRIM2 expression was confirmed in CRC cells and tumor samples.
  • TRIM2 knockdown and curcumin administration suppressed CRC cell migration and proliferation.
  • mTOR pathway activation was dampened by TRIM2 depletion, reducing AKT and S6K/4EBP1 phosphorylation.
  • Partial reversal of curcumin's effects was observed upon mTOR pathway activation.

Conclusions:

  • Curcumin inhibits colorectal cancer (CRC) onset and progression by downregulating TRIM2 and suppressing mTOR pathway activity.
  • TRIM2 plays a critical role in CRC proliferation and migration via the mTOR signaling pathway.
  • TRIM2 may serve as a potential prognostic marker for colorectal cancer (CRC).
Keywords:
Colorectal cancerCurcuminTRIM2mTOR

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