Mitochondrial membrane potential (ΔΨ(mt)) in the coordination of p53- independent proliferation and apoptosis pathways in human colonic carcinoma cells

Barbara G. Heerdt, Michele A. Houston, Gillian M. Anthony, Leonard H. Augenlicht

Research output: Contribution to journalArticle

78 Scopus citations


We have previously defined depressed mitochondrial function as a determinant in colon cancer risk and progression and established that metabolism of butyrate, a short-chain fatty acid generated during the fermentation of fiber by endogenous intestinal bacteria, induces mitochondrial function-dependent growth arrest and apoptosis of colonic carcinoma cells in vitro. Here, we dissect the relationships among mitochondrial function, growth arrest, and apoptosis, reporting that initiation and maintenance of butyrate-mediated p53-independent p21(WAF1/Cip1) induction and subsequent G0/G1 arrest require an intact mitochondrial membrane potential (ΔΨ(mt)) and that the process of dissipation of the ΔΨ(mt) is then essential for initiation of a butyrate- induced apoptotic cascade. Thus, we hypothesize that mitochondria play a pivotal role in coordinating proliferation and apoptosis pathways, a coordination that must be tightly regulated in rapidly renewing tissues, such as the colonic mucosa.

Original languageEnglish (US)
Pages (from-to)2869-2875
Number of pages7
JournalCancer Research
Issue number13
Publication statusPublished - Jul 1 1998


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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