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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 #373972
Research Project: Modification of Diurnal Patterns to Promote Health in Models for Human Metabolic Dysfunction

Location: Dietary Prevention of Obesity-related Disease Research

Title: Superior inhibitory efficacy of butyrate over propionate and acetate against human colon cancer cell proliferation via cell cycle arrest and apoptosis

Author
item Zeng, Huawei
item HAMLIN, STEPHANIE - University Of North Dakota
item Safratowich, Bryan
item CHENG, WEN-HSING - Mississippi State University
item JOHNSON, LUANN - Former ARS Employee

Submitted to: Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/17/2020
Publication Date: 8/22/2020
Citation: Zeng, H., Hamlin, S.K., Safratowich, B.D., Cheng, W., Johnson, L.K. 2020. Superior inhibitory efficacy of butyrate over propionate and acetate against human colon cancer cell proliferation via cell cycle arrest and apoptosis. Nutrition Research. 83:63-72. https://doi.org/10.1016/j.nutres.2020.08.009.
DOI: https://doi.org/10.1016/j.nutres.2020.08.009

Interpretive Summary: Colon cancer accounts for approximately 140,000 new cancer cases and 50,000 deaths each year in the US, and it is predicted that half the Western population will develop at least one colon tumor by the age of 70 years. Recent studies have shown that consumption of high fiber diets may protect against colon cancer. These effects may be due to the increased production of the short chain fatty acids (SCFAs), acetate, propionate and butyrate, generated during dietary fiber fermentation in the colon. We hypothesize that butyrate exhibits a stronger inhibitory potential against colon cancer cell proliferation compared with acetate and propionate. In the present study, we demonstrate a greater inhibitory efficacy of butyrate over propionate and acetate against human colon cancer cell proliferation. These data suggest that the metabolites of dietary fiber may protect against colon cancer by reducing cancer cell proliferation. The information will be useful for scientists and health-care professionals who are interested in dietary fiber intake and colon cancer prevention.

Technical Abstract: Intake of dietary fiber may protect against colon cancer. This effect may be due to the increased production of short chain fatty acids (SCFAs), including acetate, propionate and butyrate, during dietary fiber fermentation in the colon. To test the hypothesis that butyrate exhibits a stronger inhibitory potential against colon cancer cell proliferation compared with acetate and propionate, we determined the half maximal inhibitory concentrations (IC50) of SCFAs in HCT116 human colon cancer cell proliferation by examining cell growth curves. At 24- and 48-hr time points, IC50 (mM) concentrations of acetate, propionate and butyrate were [66.0 and 29.0], [9.2 and 3.6] and [2.5 and 1.3], respectively. Consistent with the greater anti-proliferative effect, butyrate exhibits > 3-fold stronger potential for inducing cell cycle arrest at the G2 phase with a drop in S-phase fraction (including c-Myc /p21 signaling) and apoptosis when compared with acetate and propionate. Subsequently, we focused on the effect of butyrate on apoptotic gene expression. Using a PCR array analysis, we identified 17 pro-apoptotic genes, 6 anti-apoptotic genes, and 4 cellular mediator genes with > 1-fold increase or decrease in mRNA levels out of 93 apoptosis related genes in butyrate-treated HCT116 cells when compared with untreated HCT116 cells. These genes were mainly involved in the TNF, NF'B, CARD and BCL-2 regulated pathways. Taken together, we demonstrated a greater inhibitory efficacy of butyrate over propionate and acetate against human colon cancer cell proliferation via cell cycle arrest and apoptosis.