| 9661904 |
Heerdt BG, Houston MA, Anthony GM, Augenlicht LH: Mitochondrial membrane potential (delta psi (mt)) in the coordination of p53-independent proliferation and apoptosis pathways in human colonic carcinoma cells. Cancer Res. 1998 Jul 1;58(13):2869-75.
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 p21WAF1/Cip1 induction and subsequent G0/G1 arrest require an intact mitochondrial membrane potential (delta psi (mt)) and that the process of dissipation of the delta psi (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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