Preventive Effect of Butyrate in Colon Cancer Cell Metabolism

Area of Science:

• Cancer Biology
• Metabolic Reprogramming
• Colorectal Cancer Therapeutics

Background:

• Colorectal cancer cells exhibit metabolic reprogramming, often increasing glycolysis (Warburg effect) to fuel growth.
• Butyrate, a short-chain fatty acid and histone deacetylase inhibitor, influences cancer cell differentiation and apoptosis.
• Understanding butyrate's metabolic impact is crucial for developing targeted colorectal cancer therapies.

Purpose of the Study:

• To investigate the effects of butyrate on the metabolic phenotype of three distinct colorectal cancer cell lines.
• To assess how butyrate influences glucose uptake, transporter expression, lactate production, and Krebs cycle activity.
• To explore the heterogeneity of metabolic responses to butyrate in colorectal cancer models.

Main Methods:

• Assessed [18F]FDG uptake and lactate production.
• Analyzed glucose transporter (GLUT1, 3, 5, 12) expression via flow cytometry.
• Utilized NMR isotopomer profiling to study Krebs cycle and glycolysis coupling.

Main Results:

• Butyrate decreased [18F]FDG uptake and enhanced oxidative metabolism in C2BBe1 and WiDr cells, counteracting the Warburg effect.
• LS1034 cells showed increased [18F]FDG uptake and reduced GLUT5 expression, indicating a divergent metabolic response.
• Metabolic handling of butyrate differed among cell lines, suggesting cell-specific responses and potential cytotoxic stress in LS1034.

Conclusions:

• Butyrate exerts cell-line-dependent effects on colorectal cancer cell metabolism.
• In C2BBe1 and WiDr cells, butyrate attenuated Warburg-like features; LS1034 cells showed a distinct response.
• These findings highlight the heterogeneity of metabolic responses and support butyrate's potential as a colorectal cancer modulator.