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

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.