title: Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells.
abstract: Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous cells through regulating apoptosis and cellular-signaling pathways. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiologically relevant doses of butyrate. Cellular responses to butyrate were characterized by Western analysis, fluorescent microscopy, acetylation, and DNA fragmentation analyses. Butyrate inhibited cell proliferation, and 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.
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USA. huawei.zeng@ars.usda.gov.
authors.forename: Huawei
authors.initials: H
authors.lastname: Zeng
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USA. dtaussig@gmail.com.
authors.forename: David P
authors.initials: DP
authors.lastname: Taussig
authors.affiliation: Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Starkville, MS 39762, USA. wcheng@fsnhp.msstate.edu.
authors.forename: Wen-Hsing
authors.initials: WH
authors.lastname: Cheng
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203, USA. luann.johnson@ars.usda.gov.
authors.forename: LuAnn K
authors.initials: LK
authors.lastname: Johnson
authors.affiliation: Departments of Dietetics and Nutrition, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. RHakkak@uams.edu.|Arkansas Children Research Institute, Little Rock, AR 72202, USA. RHakkak@uams.edu.
authors.forename: Reza
authors.initials: R
authors.lastname: Hakkak
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D015398:Signal Transduction
chemical_list: D016588:Anticarcinogenic Agents; D002087:Butyrates
keywords: apoptosis; butyrate; cell proliferation; colon cancer; microbiota