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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #416000
Research Project: Modification of Diurnal Patterns to Promote Health in Models for Human Metabolic Dysfunction

Location: Dietary Prevention of Obesity-related Disease Research

Title: The protective potential of butyrate against colon cancer cell migration and invasion is critically dependent on cell type

Author
item ONCEL, SEMA - Oak Ridge Institute For Science And Education (ORISE)
item Safratowich, Bryan
item Zeng, Huawei

Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/11/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: Colorectal cancer (CRC) is the second most common cause of cancer death in men and women in the United States. In 2023, approximately 153, 020 individuals will be di-agnosed with CRC and 52,550 will die from the disease. It has been reported that consuming high levels of dietary fiber (e.g., > 38 g / day, a male US adult) reduces the risk of colon cancer in human populations and animal models. However, the mechanism underlying this observation remains to be determined. In this study, we demonstrate that inhibitory efficacy of dietary fiber metabolites (e.g., butyrate) against human colon cancer cell migration and invasion is cell-type specific in a human colon cell model. The information will be useful for scientists and health-care professionals who are interested in diet and healthy gut.

Technical Abstract: 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. We hypothesize the effectiveness of butyrate on reducing colon cancer cell migration and invasion may vary due to the cell-type. Methods and results: We determined the efficacy of butyrate (0 to 4 mM) to inhibit cancer cell migration, invasion, and related signaling proteins in three distinct human colorectal cancer (CRC) HCT116, HT-29, and Caco-2 cell lines. Butyrate exhibited a dose-dependent inhibitory effect on cancer cell migration and invasion. This inhibitory potential on oncogenic FAK and 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 the public cancer database demonstrated 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.