MITOCHONDRIAL-MEMBRANE POTENTIAL (DELTA-PSI(MT)) IN THE COORDINATION OF P53-INDEPENDENT PROLIFERATION AND APOPTOSIS PATHWAYS IN HUMAN COLONIC-CARCINOMA CELLS
Bg. Heerdt et al., MITOCHONDRIAL-MEMBRANE POTENTIAL (DELTA-PSI(MT)) IN THE COORDINATION OF P53-INDEPENDENT PROLIFERATION AND APOPTOSIS PATHWAYS IN HUMAN COLONIC-CARCINOMA CELLS, Cancer research, 58(13), 1998, pp. 2869-2875
We have previously defined depressed mitochondrial function as a deter
minant in colon cancer risk and progression and established that metab
olism of butyrate, a short-chain fatty acid generated during the ferme
ntation of fiber by endogenous intestinal bacteria, induces mitochondr
ial function-dependent growth arrest and apoptosis of colonic carcinom
a cells in vitro. Here, we dissect the relationships among mitochondri
al function, growth arrest, and apoptosis, reporting that initiation a
nd maintenance of butyrate-mediated p53-independent p21(WAF1/Cip1) ind
uction and subsequent G(0)/G(1) arrest require an intact mitochondrial
membrane potential (Delta Psi(mt)) and that the process of dissipatio
n 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 tiss
ues, such as the colonic mucosa.