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Butyrate Plays Differential Roles in Cellular Signaling in Cancerous HCT116 and Noncancerous NCM460 Colon Cells
Author(s) -
Zeng Huawei,
Taussig David P,
Cheng WenHsing,
Hakkak Reza
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.688.9
Subject(s) - butyrate , apoptosis , signal transduction , dna fragmentation , microbiology and biotechnology , acetylation , chemistry , histone , biology , sodium butyrate , cell growth , cancer research , programmed cell death , cell culture , biochemistry , dna , fermentation , gene , genetics
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. Support or Funding Information This work was supported by USDA‐ARS, CRIS project (5450‐51000‐050‐00D).