Abstract
Objectives
Intake of fiber has beneficial properties for gut health. These effects may be due to the increased production of short chain fatty acids (SCFAs) such as acetate, propionate and butyrate during dietary fiber fermentation in the colon. We tested the hypothesis that butyrate exhibits a stronger inhibitory potential against colon cancer cell proliferation compared with acetate and propionate.
Methods
With a human HCT116 colon cancer cell culture model, we used cell cycle, apoptosis, PCR array, biochemical, western blotting and immunofluorescent assays to determine SCFAs’ inhibitory effects on HCT116 cell proliferation.
Results
We determined the half maximal inhibitory concentrations (IC50) of SCFAs in HCT116 cell proliferation by examining cell growth curves. At 24- and 48- hour 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 (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 tumor necrosis factor alpha receptor, NFκB, caspase recruitment domain-containing protein and B-cell lymphoma-2 regulated pathways.
Conclusions
Collectively, we demonstrated a greater inhibitory efficacy of butyrate over propionate and acetate against human colon cancer cell proliferation via cell cycle arrest and apoptosis.
Funding Sources
This work was supported by U.S. Department of Agriculture, Agricultural Research Service, research project 3062–51,000-056–00D.
CBX3 promotes colon cancer cell proliferation by CDK6 kinase-independent function during cell cycle