TY - JOUR
T1 - Mitochondrial membrane potential (ΔΨ(mt)) in the coordination of p53- independent proliferation and apoptosis pathways in human colonic carcinoma cells
AU - Heerdt, Barbara G.
AU - Houston, Michele A.
AU - Anthony, Gillian M.
AU - Augenlicht, Leonard H.
PY - 1998/7/1
Y1 - 1998/7/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 9661904
AN - SCOPUS:0032127373
VL - 58
SP - 2869
EP - 2875
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 13
ER -