Short-chain fatty acid-initiated cell cycle arrest and apoptosis of colonic epithelial cells is linked to mitochondrial function

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

Research output: Contribution to journalArticlepeer-review

175 Scopus citations

Abstract

Butyrate, a short-chain fatty acid produced during microbial fermentation of fiber, induces growth arrest, differentiation, and apoptosis of colonic epithelial cells in vitro, and our prior work has shown that this induction is tightly linked to mitochondrial activity. Here we demonstrate that 12 h following induction, SW620 human colonic carcinoma cells accumulate simultaneously in G0-G1 nd G2-M of the cell cycle. Four h later, during this G0-G1 to G2-M arrest, cells begin to undergo apoptosis. Using a series of unrelated agents that modulate mitochondrial functions, we demonstrate that mitochondrial electron transport and membrane potential are critical in initiation of this butyrate-mediated growth arrest and apoptosis. Colonic tumorigenesis is characterized by abnormalities in proliferation, apoptosis, and mitochondrial activities. Thus, butyrate may reduce risk for colon cancer by inducing a pathway that enhances mitochondrial function, ultimately resulting in initiation of growth arrest and apoptosis of colonic epithelial cells.

Original languageEnglish (US)
Pages (from-to)523-532
Number of pages10
JournalCell Growth and Differentiation
Volume8
Issue number5
StatePublished - May 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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