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[Cancer Research 54, 3288-3294, June 15, 1994]
© 1994 American Association for Cancer Research

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Potentiation by Specific Short-Chain Fatty Acids of Differentiation and Apoptosis in Human Colonic Carcinoma Cell Lines1

Barbara G. Heerdt2, Michele A. Houston and Leonard H. Augenlicht

Department of Oncology, Albert Einstein Cancer Center, Bronx, New York 10467

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.

1 This work was supported in part by American Institute for Cancer Research Grant 92A05, National Cancer Institute Grant P30-CA-1330, and a grant from the Aaron Diamond Foundation.

2 To whom requests for reprints should be addressed, at Department of Oncology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467.

Received 1/27/94. Accepted 4/20/94.




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Am. J. Physiol. Gastrointest. Liver Physiol.Home page
B. A. Jones and G. J. Gores
Physiology and pathophysiology of apoptosis in epithelial cells of the liver, pancreas, and intestine
Am J Physiol Gastrointest Liver Physiol, December 1, 1997; 273(6): G1174 - G1188.
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Mol. Pharmacol.Home page
L. A. Parsels, R. C. Zellars, T. L. Loney, J. D. Parsels, M. F. Clarke, A. K. Merchant, T. S. Lawrence, and J. Maybaum
Prevention of Fluorodeoxyuridine-Induced Cytotoxicity and DNA Damage in HT29 Colon Carcinoma Cells by Conditional Expression of Wild-Type p53 Phenotype
Mol. Pharmacol., October 1, 1997; 52(4): 600 - 605.
[Abstract] [Full Text]


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J. Cell Sci.Home page
R. Fitzgerald, M. Omary, and G Triadafilopoulos
Acid modulation of HT29 cell growth and differentiation. An in vitro model for Barrett's esophagus
J. Cell Sci., January 3, 1997; 110(5): 663 - 671.
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J. Nutr.Home page
H. M. Aukema, L. A. Davidson, B. C. Pence, Y.-H. Jiang, J. R. Lupton, and R. S. Chapkin
Butyrate Alters Activity of Specific cAMP-Receptor Proteins in a Transgenic Mouse Colonic Cell Line
J. Nutr., January 1, 1997; 127(1): 18 - 24.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
D. Courilleau, E. Chastre, M. Sabbah, G. Redeuilh, A. Atfi, and J. Mester
B-ind1, a Novel Mediator of Rac1 Signaling Cloned from Sodium Butyrate-treated Fibroblasts
J. Biol. Chem., June 2, 2000; 275(23): 17344 - 17348.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
C. S. Peters, X. Liang, S. Li, S. Kannan, Y. Peng, R. Taub, and R. H. Diamond
ATF-7, a Novel bZIP Protein, Interacts with the PRL-1 Protein-tyrosine Phosphatase
J. Biol. Chem., April 20, 2001; 276(17): 13718 - 13726.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
J. Yang, Y. Kawai, R. W. Hanson, and I. J. Arinze
Sodium Butyrate Induces Transcription from the Galpha i2 Gene Promoter through Multiple Sp1 Sites in the Promoter and by Activating the MEK-ERK Signal Transduction Pathway
J. Biol. Chem., July 6, 2001; 276(28): 25742 - 25752.
[Abstract] [Full Text] [PDF]




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