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 p21WAF1/Cip1 induction and subsequent G0/G1 arrest require an intact mitochondrial membrane potential (ΔΨmt) and that the process of dissipation of the ΔΨmt 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.
Footnotes
-
↵1 This work was supported in part by National Cancer Institute Grants R29 CA59932, RO1 CA75246, and PO CA 13330 and American Institute for Cancer Research Grant 95B025.
-
↵2 To whom requests for reprints should be addressed, at Albert Einstein Cancer Center, Montefiore Medical Center, Department of Oncology/Hofheimer 511, 111 East 210th Street, Bronx, NY 10467. Phone: (718) 920-2750; Fax: (718) 882-4464.
- Received January 6, 1998.
- Accepted April 30, 1998.
- ©1998 American Association for Cancer Research.
Volume 58, Issue 13
