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Isoeugenol Inhibits Growth, Migration, and Invasion in Colorectal Cancer Cells With Distinct Molecular

Zih-Shuan Liou1, Chih-Chun Kuo2, Chien-Chih Yeh3,4

  • 1Department of Life Sciences, National Central University, Taoyuan, Taiwan.

Molecular Nutrition & Food Research
|April 16, 2026
PubMed

Insights

Piper betle isoeugenol inhibits colorectal cancer cell growth, migration, and invasion. These effects are mediated by activating AMPK and p38 MAPK pathways, impacting cell cycle and EMT regulation.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide.
  • Herbal compounds show potential in regulating CRC development, but specific pathways remain underexplored.
  • Piper betle isoeugenol's role in CRC cells (CRCCs) signaling is largely unknown.

Purpose of the Study:

  • To investigate the effects and underlying mechanisms of Piper betle isoeugenol on colorectal cancer cell lines.
  • To elucidate the signal pathways modulated by isoeugenol in CRCCs.

Main Methods:

  • Utilized three distinct CRC cell lines (SW480, SW620, HCT116) as in vitro models.
  • Performed wound healing and Boyden chamber assays to assess cell migration and invasion.
  • Analyzed key proteins involved in cell cycle regulation, epithelial-mesenchymal transition (EMT), and matrix metalloproteinases (MMPs).
  • Investigated the role of AMPK and p38 MAPK pathways via pharmacological inhibition.

Main Results:

  • Isoeugenol significantly inhibited CRCC growth, migration, and invasion.
  • Isoeugenol suppressed cell cycle regulators (e.g., pAKT, CDK4/6, cyclin D1) and EMT markers (e.g., N-cadherin, Snail).
  • Isoeugenol increased levels of pAMPK, pJNK, pp38 MAPK, and E-cadherin, and inhibited MMP-2/9 activity.
  • AMPK or p38 MAPK inhibition counteracted the anti-cancer effects of isoeugenol.

Conclusions:

  • Isoeugenol demonstrates potent anti-cancer properties against colorectal cancer cells in vitro.
  • Isoeugenol exerts its effects by activating AMPK and p38 MAPK pathways.
  • Isoeugenol modulates critical pathways regulating cell cycle progression and epithelial-mesenchymal transition, offering potential therapeutic strategies for CRC.
Keywords:
colorectal cancer cellsgrowthinvasionisoeugenolmigration

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