Chemoprevention of intestinal tumorigenesis by nabumetone: induction of apoptosis and Bcl-2 downregulation.
Treatment of MIN mice with the nonsteroidal anti-inflammatory drug, nabumetone, resulted in a dose-dependent suppression of intestinal tumorigenesis. In both the uninvolved MIN mouse colonic epithelium and HT-29 colon cancer cells, nabumetone downregulated the anti-apoptotic protein, Bcl-2, with concomitant induction of apoptosis, suggesting a potential mechanism for colon cancer chemoprevention.
Roy
H K
HK
Department of Internal Medicine, University of Nebraska Medical Center/Eppley Cancer Institute, 982000 Nebraska Medical Center, Omaha, NE 68198-2000, USA
Karoski
W J
WJ
Ratashak
A
A
Smyrk
T C
TC
D011125:Adenomatous Polyposis Coli / Q000235:genetics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002074:Butanones / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D019254:Genes, bcl-2; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008817:Mice, Mutant Strains; D000077430:Nabumetone; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D002074:Butanones; D019253:Proto-Oncogene Proteins c-bcl-2; D000077430:Nabumetone