Piperine suppresses the Wnt/β-catenin pathway and has anti-cancer effects on colorectal cancer cells

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Wnt/β-catenin signaling pathway is frequently dysregulated in over 94% of colorectal cancer (CRC) cases.
• Mutations in APC or CTNNB1 (β-catenin) lead to pathway overactivation, driving intestinal hyperplasia and cancer development.
• Piperine, a natural alkaloid from black pepper, possesses known pharmacological properties, but its anti-cancer mechanisms require further elucidation.

Purpose of the Study:

• To investigate the molecular mechanisms by which piperine affects the Wnt/β-catenin signaling pathway.
• To evaluate the anti-cancer effects of piperine on colorectal cancer cell lines.
• To determine if piperine's effects are specific to cancer cells.

Main Methods:

• Utilized Wnt/β-catenin pathway epistasis experiments to assess piperine's impact on pathway components.
• Quantified β-catenin nuclear localization in HCT116 colorectal cancer cells.
• Assessed cell proliferation and migration in multiple colorectal cancer cell lines (HCT116, SW480, DLD-1) and a non-tumoral cell line (IEC-6).

Main Results:

• Piperine was demonstrated to inhibit the canonical Wnt pathway, including when induced by overexpressed β-catenin, β-catenin S33A, or dnTCF4 VP16.
• Piperine suppressed β-catenin nuclear localization in HCT116 cells.
• Piperine significantly impaired proliferation and migration in HCT116, SW480, and DLD-1 colorectal cancer cell lines, but not in the non-tumoral IEC-6 cell line.

Conclusions:

• Piperine effectively inhibits the canonical Wnt signaling pathway.
• Piperine exhibits significant anti-cancer effects on colorectal cancer cell lines by impeding proliferation and migration.
• Piperine represents a potential therapeutic agent for colorectal cancer, warranting further investigation into its molecular actions.