Carcinogenesis Advance Access published online on September 1, 2005
Carcinogenesis, doi:10.1093/carcin/bgi221
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1 Division of Cancer Prevention, Department of Medicine, SUNY at Stony Brook, Stony Brook, NY 11794-5200, USA
* To whom correspondence should be addressed. Nitric oxide donating aspirin (NO-ASA), consisting of a traditional ASA to which a NO-releasing moiety is covalently attached, is a promising chemoprevention agent against colon cancer. Its mechanism of action is not fully delineated. Here we examined its effect on the expression of the nuclear receptor PPAR
Received June 28, 2005
Revised August 8, 2005
Accepted August 30, 2005
CANCER BIOLOGY
NO-donating aspirin isomers downregulate peroxisome proliferator-activated receptor (PPAR)
expression in APCmin/+ mice proportionally to their tumor inhibitory effect: implications for the role of PPAR in carcinogenesis
Basil Rigas, E-mail: basil.rigas{at}stonybrook.edu
Abstract 
, whose role in colon carcinogenesis remains highly controversial. We studied histochemically the effect of the meta and para positional isomers of NO-ASA on PPAR expression in Min and wild type mice and on cell proliferation and apoptosis. PPAR, minimally expressed in wild type mice, was significantly expressed in Min mice. para NO-ASA inhibited intestinal tumor incidence (59%) and PPAR expression (55.3%) more than meta (38% and 41.5%, respectively). Neither isomer affected cell proliferation, but both induced apoptosis in Min mice (para 52.5% for normal mucosa and 70.3%, for tumors; meta 31.4% and 21.9% respectively). The changes in PPAR expression correlated significantly with changes in apoptosis. Furthermore, NO-ASA induced areas of necrosis in intestinal tumors likely resulting from the induction of atypical apoptosis. Our data suggest that NO-ASA suppresses intestinal tumorigenesis possibly in part through its inhibitory effect on PPAR, the expression of which may contribute to intestinal carcinogenesis.
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