|TAUSSIG, DAVID - Former ARS Employee|
|CHENG, WEN-HSING - Mississippi State University|
|JOHNSON, LUANN - University Of North Dakota|
|HAKKAK, REZA - University Of Arkansas|
Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/23/2016
Publication Date: 1/1/2017
Publication URL: http://handle.nal.usda.gov/10113/5642494
Citation: Zeng, H., Taussig, D., Cheng, W., Johnson, L., Hakkak, R. 2017. Butyrate inhibits cancerous HCT116 cell proliferation but to a lesser extent in noncancerous NCM460 colon cells. Nutrients. 9(1):25-38.
Interpretive Summary: Many epidemiological and experimental studies indicate that dietary fiber intake is inversely associated with colon cancer risk. Butyrate, a major metabolite in colonic lumen arising from gut bacterial fermentation of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate at the cellular level remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous colon cells. In our present study, we tested this hypothesis by exposing cancerous or non-cancerous colon cells to physiologically relevant doses of butyrate, and found that butyrate activated the “survival signaling” in noncancerous colon cells while inhibiting the “survival signaling” in cancerous colon cells. Overall, butyrate has a minimal effect on noncancerous colon cells but a strong inhibitory effect on cell proliferation in cancerous colon cells. Our data provide the mechanistic basis concerning the selective potential of butyrate’s anti-colon cancer property. The information will be useful for scientists and health-care professionals who are interested in dietary fiber intake and cancer prevention.
Technical Abstract: Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate at the cellular level remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous colon cells through signaling pathways regulating apoptosis and cellular survival. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiologically relevant doses of butyrate (0.25-2 mmol/L). Cellular responses to butyrate were characterized by Western analysis of protein levels, fluorescent microscopy, acetylation, and DNA fragmentation analyses. Upon exposure to butyrate (2 mmol/L) for 48 hours, cell proliferation was reduced by 84% in HCT116 cells, compared to 47% in NCM460 cells. Similarly, butyrate led to an induction of apoptosis, genomic DNA fragmentation in HCT116 cells, but to a lesser extent in NCM460 cells. Although butyrate increased H3 histone deacetylation and p21 tumor suppressor expression in both cell types, p21 protein level was greater with intense expression around the nuclei in HCT116 cells when compared with that in NCM460 cells. Furthermore, butyrate treatment increased the phosphorylation of extracellular-regulated kinase 1/2 (p-ERK1/2), a survival signal, in NCM460 cells while it decreased p-ERK1/2 in HCT116 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic potential in HCT116 cells may confer the increased sensitivity of cancerous colon cells to butyrate in comparison with noncancerous colon cells.