Cargando…

Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells

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 noncancerou...

Descripción completa

Detalles Bibliográficos
Autores principales: Zeng, Huawei, Taussig, David P., Cheng, Wen-Hsing, Johnson, LuAnn K., Hakkak, Reza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295069/
https://www.ncbi.nlm.nih.gov/pubmed/28045428
http://dx.doi.org/10.3390/nu9010025
_version_ 1782505359006498816
author Zeng, Huawei
Taussig, David P.
Cheng, Wen-Hsing
Johnson, LuAnn K.
Hakkak, Reza
author_facet Zeng, Huawei
Taussig, David P.
Cheng, Wen-Hsing
Johnson, LuAnn K.
Hakkak, Reza
author_sort Zeng, Huawei
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5295069
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-52950692017-02-10 Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells Zeng, Huawei Taussig, David P. Cheng, Wen-Hsing Johnson, LuAnn K. Hakkak, Reza Nutrients Article 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. MDPI 2017-01-01 /pmc/articles/PMC5295069/ /pubmed/28045428 http://dx.doi.org/10.3390/nu9010025 Text en © 2017 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zeng, Huawei
Taussig, David P.
Cheng, Wen-Hsing
Johnson, LuAnn K.
Hakkak, Reza
Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells
title Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells
title_full Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells
title_fullStr Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells
title_full_unstemmed Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells
title_short Butyrate Inhibits Cancerous HCT116 Colon Cell Proliferation but to a Lesser Extent in Noncancerous NCM460 Colon Cells
title_sort butyrate inhibits cancerous hct116 colon cell proliferation but to a lesser extent in noncancerous ncm460 colon cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295069/
https://www.ncbi.nlm.nih.gov/pubmed/28045428
http://dx.doi.org/10.3390/nu9010025
work_keys_str_mv AT zenghuawei butyrateinhibitscanceroushct116coloncellproliferationbuttoalesserextentinnoncancerousncm460coloncells
AT taussigdavidp butyrateinhibitscanceroushct116coloncellproliferationbuttoalesserextentinnoncancerousncm460coloncells
AT chengwenhsing butyrateinhibitscanceroushct116coloncellproliferationbuttoalesserextentinnoncancerousncm460coloncells
AT johnsonluannk butyrateinhibitscanceroushct116coloncellproliferationbuttoalesserextentinnoncancerousncm460coloncells
AT hakkakreza butyrateinhibitscanceroushct116coloncellproliferationbuttoalesserextentinnoncancerousncm460coloncells