Bg. Heerdt et al., SHORT-CHAIN FATTY ACID-INITIATED CELL-CYCLE ARREST AND APOPTOSIS OF COLONIC EPITHELIAL-CELLS IS LINKED TO MITOCHONDRIAL-FUNCTION, Cell growth & differentiation, 8(5), 1997, pp. 523-532
Butyrate, a short-chain fatty acid produced during microbial fermentat
ion of fiber, induces growth arrest, differentiation, and apoptosis of
colonic epithelial cells in vitro, and our prior work has shown that
this induction is tightly linked to mitochondrial activity, Here we de
monstrate that 12 h following induction, SW620 human colonic carcinoma
cells accumulate simultaneously in G(0)-G(1) and G(2)-M of the cell c
ycle. Four h later, during this C-0-G(1) to G(2)-M arrest, cells begin
to undergo apoptosis, Using a series of unrelated agents that modulat
e mitochondrial functions, we demonstrate that mitochondrial electron
transport and membrane potential are critical in initiation of this bu
tyrate-mediated growth arrest and apoptosis. Colonic tumorigenesis is
characterized by abnormalities in proliferation, apoptosis, and mitoch
ondrial activities. Thus, butyrate may reduce risk for colon cancer by
inducing a pathway that enhances mitochondrial function, ultimately r
esulting in initiation of growth arrest and apoptosis of colonic epith
elial cells.