The Protective Potential of Butyrate against Colon Cancer Cell Migration and Invasion Is Critically Dependent on Cell Type

Scope Short‐chain fatty acids such as butyrate are produced through the fermentation of dietary fiber by colonic bacteria. Preclinical studies indicate an anticancer potential of butyrate, but clinical evidence shows greater variability. The study hypothesizes the effectiveness of butyrate on reducing colon cancer cell migration and invasion may vary due to the cell‐type. Methods and results The study determines the efficacy of butyrate (0–4 mM) to inhibit cancer cell migration, invasion, and related signaling proteins in three distinct human colorectal cancer (CRC) cell lines: HCT116, HT‐29, and Caco‐2. Butyrate exhibits a dose‐dependent inhibitory effect on cancer cell migration and invasion. This inhibitory potential on oncogenic focal adhesion kinase (FAK) and sarcoma (Src) proteins is greater in HCT116 cells (1.1 and 0.8‐fold) and HT‐29 cells (0.9 and 0.4‐fold) compared to Caco‐2 cells, respectively. Conversely, E‐cadherin protein, a classical epithelial cell marker and potential tumor suppressor, is 2.3‐fold greater in HCT116 cells than in HT‐29 cells and Caco‐2 cells. Moreover, survival analysis from a public cancer database demonstrates that CRC patients with high E‐cadherin expression have a 13% greater 5‐year survival rate than those with low expression. Conclusion Collectively, butyrate's anti‐cancer efficacy on CRC cells varies depending on cell‐type and is linked to the FAK/Src/E‐cadherin pathway.