Potentiation by specific short-chain fatty acids of differentiation and apoptosis in human colonic carcinoma cell lines

Barbara G. Heerdt, Michele A. Houston, Leonard H. Augenlicht

Research output: Contribution to journalArticle

347 Citations (Scopus)

Abstract

The architecture of normal colonic mucosa suggests that terminally differentiated epithelial cells near the top of the crypt are extruded into the colonic lumen. Morphological studies have identified apoptotic cells among the differentiated phenotypes near the crypt-lumen interface, suggesting a link between pathways of differentiation, apoptosis, and cellular shedding. We studied these processes in HT29 and SW620 cells and found that compared to adherent cells, those cells which were shed during standard, uninduced culture conditions exhibited nonrandom DNA fragmentation characteristic of apoptosis. Moreover, these apoptotic cells, which accumulate in the media, exhibited a more differentiated phenotype. Because short-chain fatty acids (SCFAs) are natural effectors of colonic cell differentiation in vivo, we investigated the specificity of three 4-carbon atom SCFAs on potentiating differentiation and apoptosis, and thus accumulation of shed cells in the conditioned media, in these colonic carcinoma cell lines. Whereas the unbranched SCFA butyrate induced a more differentiated phenotype and enhanced apoptosis, two derivatives of butyrate, branched isobutyric acid and a nonmetabolizable fluorine-substituted analogue, heptafluorobutyric acid, were ineffective in inducing either differentiation or apoptosis. Thus, potentiated differentiation and apoptosis in colonic carcinoma cells were linked to SCFA structure and, most likely, utilization.

Original languageEnglish (US)
Pages (from-to)3288-3294
Number of pages7
JournalCancer Research
Volume54
Issue number12
StatePublished - Jun 15 1994

Fingerprint

Volatile Fatty Acids
Apoptosis
Carcinoma
Cell Line
Butyrates
Phenotype
HT29 Cells
Fluorine
DNA Fragmentation
Conditioned Culture Medium
Cell Differentiation
Mucous Membrane
Carbon
Epithelial Cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Potentiation by specific short-chain fatty acids of differentiation and apoptosis in human colonic carcinoma cell lines. / Heerdt, Barbara G.; Houston, Michele A.; Augenlicht, Leonard H.

In: Cancer Research, Vol. 54, No. 12, 15.06.1994, p. 3288-3294.

Research output: Contribution to journalArticle

@article{cd82182fbd33461c84282cec4eb3e150,
title = "Potentiation by specific short-chain fatty acids of differentiation and apoptosis in human colonic carcinoma cell lines",
abstract = "The architecture of normal colonic mucosa suggests that terminally differentiated epithelial cells near the top of the crypt are extruded into the colonic lumen. Morphological studies have identified apoptotic cells among the differentiated phenotypes near the crypt-lumen interface, suggesting a link between pathways of differentiation, apoptosis, and cellular shedding. We studied these processes in HT29 and SW620 cells and found that compared to adherent cells, those cells which were shed during standard, uninduced culture conditions exhibited nonrandom DNA fragmentation characteristic of apoptosis. Moreover, these apoptotic cells, which accumulate in the media, exhibited a more differentiated phenotype. Because short-chain fatty acids (SCFAs) are natural effectors of colonic cell differentiation in vivo, we investigated the specificity of three 4-carbon atom SCFAs on potentiating differentiation and apoptosis, and thus accumulation of shed cells in the conditioned media, in these colonic carcinoma cell lines. Whereas the unbranched SCFA butyrate induced a more differentiated phenotype and enhanced apoptosis, two derivatives of butyrate, branched isobutyric acid and a nonmetabolizable fluorine-substituted analogue, heptafluorobutyric acid, were ineffective in inducing either differentiation or apoptosis. Thus, potentiated differentiation and apoptosis in colonic carcinoma cells were linked to SCFA structure and, most likely, utilization.",
author = "Heerdt, {Barbara G.} and Houston, {Michele A.} and Augenlicht, {Leonard H.}",
year = "1994",
month = "6",
day = "15",
language = "English (US)",
volume = "54",
pages = "3288--3294",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "12",

}

TY - JOUR

T1 - Potentiation by specific short-chain fatty acids of differentiation and apoptosis in human colonic carcinoma cell lines

AU - Heerdt, Barbara G.

AU - Houston, Michele A.

AU - Augenlicht, Leonard H.

PY - 1994/6/15

Y1 - 1994/6/15

N2 - The architecture of normal colonic mucosa suggests that terminally differentiated epithelial cells near the top of the crypt are extruded into the colonic lumen. Morphological studies have identified apoptotic cells among the differentiated phenotypes near the crypt-lumen interface, suggesting a link between pathways of differentiation, apoptosis, and cellular shedding. We studied these processes in HT29 and SW620 cells and found that compared to adherent cells, those cells which were shed during standard, uninduced culture conditions exhibited nonrandom DNA fragmentation characteristic of apoptosis. Moreover, these apoptotic cells, which accumulate in the media, exhibited a more differentiated phenotype. Because short-chain fatty acids (SCFAs) are natural effectors of colonic cell differentiation in vivo, we investigated the specificity of three 4-carbon atom SCFAs on potentiating differentiation and apoptosis, and thus accumulation of shed cells in the conditioned media, in these colonic carcinoma cell lines. Whereas the unbranched SCFA butyrate induced a more differentiated phenotype and enhanced apoptosis, two derivatives of butyrate, branched isobutyric acid and a nonmetabolizable fluorine-substituted analogue, heptafluorobutyric acid, were ineffective in inducing either differentiation or apoptosis. Thus, potentiated differentiation and apoptosis in colonic carcinoma cells were linked to SCFA structure and, most likely, utilization.

AB - The architecture of normal colonic mucosa suggests that terminally differentiated epithelial cells near the top of the crypt are extruded into the colonic lumen. Morphological studies have identified apoptotic cells among the differentiated phenotypes near the crypt-lumen interface, suggesting a link between pathways of differentiation, apoptosis, and cellular shedding. We studied these processes in HT29 and SW620 cells and found that compared to adherent cells, those cells which were shed during standard, uninduced culture conditions exhibited nonrandom DNA fragmentation characteristic of apoptosis. Moreover, these apoptotic cells, which accumulate in the media, exhibited a more differentiated phenotype. Because short-chain fatty acids (SCFAs) are natural effectors of colonic cell differentiation in vivo, we investigated the specificity of three 4-carbon atom SCFAs on potentiating differentiation and apoptosis, and thus accumulation of shed cells in the conditioned media, in these colonic carcinoma cell lines. Whereas the unbranched SCFA butyrate induced a more differentiated phenotype and enhanced apoptosis, two derivatives of butyrate, branched isobutyric acid and a nonmetabolizable fluorine-substituted analogue, heptafluorobutyric acid, were ineffective in inducing either differentiation or apoptosis. Thus, potentiated differentiation and apoptosis in colonic carcinoma cells were linked to SCFA structure and, most likely, utilization.

UR - http://www.scopus.com/inward/record.url?scp=0028286187&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028286187&partnerID=8YFLogxK

M3 - Article

C2 - 8205551

AN - SCOPUS:0028286187

VL - 54

SP - 3288

EP - 3294

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 12

ER -