New Wnt/beta-catenin signaling inhibitors isolated from Eleutherine palmifolia

Area of Science:

• Pharmacognosy
• Molecular Biology
• Oncology

Background:

• Aberrant Wnt/beta-catenin signaling is linked to cancer development.
• Targeting TCF/beta-catenin transcriptional activity is a strategy for cancer therapy.

Purpose of the Study:

• To identify novel inhibitors of TCF/beta-catenin transcriptional activity from natural sources.
• To evaluate the anti-cancer potential of compounds isolated from Eleutherine palmifolia.

Main Methods:

• Screening of plant extracts for inhibition of TCF/beta-catenin activity.
• Activity-guided fractionation and isolation of naphthalene derivatives.
• Assays for TCF/beta-catenin transcriptional inhibition, cell viability, and cytotoxicity.
• Western blot analysis to determine nuclear beta-catenin protein levels.

Main Results:

• Eleutherine palmifolia extract yielded 15 naphthalene derivatives, including 4 new compounds (eleutherinosides B-E).
• Ten compounds demonstrated significant activity and high cell viability in 293T cells.
• Compounds 2 and 9 dose-dependently inhibited TCF/beta-catenin transcription in SW480 colon cancer cells.
• Compounds 2 and 9 exhibited selective cytotoxicity against colorectal cancer cell lines.
• Compound 9 reduced nuclear beta-catenin protein levels, correlating with transcriptional inhibition.

Conclusions:

• Eleutherine palmifolia contains compounds with potent inhibitory activity against Wnt/beta-catenin signaling.
• Compounds 2 and 9 show promise as selective anti-colorectal cancer agents.
• The mechanism of action involves the reduction of nuclear beta-catenin, thereby inhibiting TCF/beta-catenin transcription.