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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 #323366

Research Project: Health Roles of Dietary Selenium in Obesity

Location: Dietary Prevention of Obesity-related Disease Research

Title: Butyrate plays differential roles in cellular signaling in cancerous HCT116 and noncancerous NCM460 colon cells

Author
item Zeng, Huawei
item Taussig, David
item Cheng, Wen-hsing - Mississippi State University
item Hakkak, Reza - University Of Arkansas

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 2/1/2016
Publication Date: 4/1/2016
Citation: Zeng, H., Taussig, D.P., Cheng, W., Hakkak, R. 2016. Butyrate plays differential roles in cellular signaling in cancerous HCT116 and noncancerous NCM460 colon cells [abstract]. Federation of American Societies for Experimental Biology Conference, April 1-6, 2016, San Diego, California. 30:688.9.

Interpretive Summary: Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects in colon. However, the mechanistic action of butyrate at the cellular level remains to be determined. We hypothesize that butyrate plays differential roles in cancerous and non-cancerous cells through signaling pathways regulating histone deacetylation, apoptosis, and cellular survival. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiological relevant doses of butyrate (0.25-2 mmol/L). Cellular responses were characterized by protein expression (Western blotting), fluorescent microscopy, acetylation, and DNA fragmentation analyses. Upon exposure to butyrate (2 mmol/L) for 72 hours, cell proliferation was reduced by 93% in HCT116 cells, compared to 57% in NCM460 cells. In addition, butyrate treatment led to an induction of apoptosis, histone deacetylation, genomic DNA fragmentation and p21 tumor suppressor expression in HCT116 cells, but to a smaller extent in NCM460 cells. In contrast, butyrate increased the phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) in NCM460 cells but not in HCT116 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic signaling in HCT116 cells may confer the increased sensitivity of cancerous colon cells to butyrate in comparison with noncancerous colon cells.

Technical Abstract: Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects in colon. However, the mechanistic action of butyrate at the cellular level remains to be determined. We hypothesize that butyrate plays differential roles in cancerous and non-cancerous cells through signaling pathways regulating histone deacetylation, apoptosis, and cellular survival. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiological relevant doses of butyrate (0.25-2 mmol/L). Cellular responses were characterized by protein expression (Western blotting), fluorescent microscopy, acetylation, and DNA fragmentation analyses. Upon exposure to butyrate (2 mmol/L) for 72 hours, cell proliferation was reduced by 93% in HCT116 cells, compared to 57% in NCM460 cells. In addition, butyrate treatment led to an induction of apoptosis, histone deacetylation, genomic DNA fragmentation and p21 tumor suppressor expression in HCT116 cells, but to a smaller extent in NCM460 cells. In contrast, butyrate increased the phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) in NCM460 cells but not in HCT116 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic signaling in HCT116 cells may confer the increased sensitivity of cancerous colon cells to butyrate in comparison with noncancerous colon cells.