Antiproliferative effects of the enantiomers of flurbiprofen.
Nonsteroidal antiinflammatory drugs (NSAIDs) are recognized for inhibiting growth of colon tumors in animal models, and for reducing the risk of colon cancer in humans. The mechanisms involved have not been established, but are thought to be related to reduced prostaglandin biosynthesis. The present study investigates the effect of COX-inhibiting and non-COX-inhibiting enantiomers of flurbiprofen on rat colonocyte proliferation. Intestinal ulceration was used as a surrogate indicator of COX inhibition. Sprague Dawley rats were treated orally with 6.3 mg/kg of R- or s-flurbiprofen or vehicle. Colonocyte labeling index and small bowel ulcer index were measured. R-flurbiprofen and S-flurbiprofen significantly reduced colonocyte labeling index, by 34% and 23% respectively, compared with vehicle. R-flurbiprofen caused minimal ulcer formation (4.48 mm2) compared with S-flurbiprofen (94.4 mm2). These findings suggest that R-flurbiprofen-mediated control of colonocyte proliferation is independent of prostaglandin biosynthesis.
McCracken
J D
JD
Division of Gastroenterology, Loma Linda University Medical Center, California 92350, USA.
Wechter
W J
WJ
Liu
Y
Y
Chase
R L
RL
Kantoci
D
D
Murray
E D
ED
Quiggle
D D
DD
Mineyama
Y
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D005480:Flurbiprofen / Q000097:blood / Q000494:pharmacology*; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology; D010437:Peptic Ulcer / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D005480:Flurbiprofen