Abstract
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 language | English (US) |
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Pages (from-to) | 2869-2875 |
Number of pages | 7 |
Journal | Cancer research |
Volume | 58 |
Issue number | 13 |
State | Published - Jul 1 1998 |
ASJC Scopus subject areas
- Oncology
- Cancer Research