Comparisons of the anti-proliferative effects of butyrate and aspirin on human colonic mucosa in vitro.
The short-chain fatty acid butyrate is regarded as a regulative agent in haemostasis of mucosal cell turnover. Inhibition of prostaglandin E2 synthesis is particularly involved in this regulation process. In the present study, proliferation was stimulated in colonic biopsies of 12 healthy subjects (age 51.3 years, range 25-81) by incubation with deoxycholic acid (5 micromol/l DCA). The anti-proliferative and cyclo-oxygenase-inhibiting properties of butyrate (10 mmol/l BUT) and of aspirin (555 micromol/l ASA) were investigated. Colonic cell proliferation was determined by bromodeoxyuridine immunohistochemistry. PGE2 release into the incubation medium was measured by radioimmunoassay. Incubation with DCA/ASA, DCA/BUT and DCA/ASA/BUT revealed a significant reduction in crypt cell proliferation as measured by the labelling index of the whole crypt in comparison to incubation with DCA alone (DCA/ASA: 0.14, P < 0.01; DCA/BUT: 0.15, P < 0.05; DCA/ASA/BUT: 0.15, P < 0.05, versus DCA: 0.18). The labelling index for the upper 40% of the crypt was only lower after incubation with DCA/ASA (0.023) compared to DCA (0.028) (P < 0.05). PGE2 release from biopsy specimens was only significantly decreased in the incubation media where ASA was added (DCA/ASA: 29.0 pg/mg mucosa/h, P < 0.005; DCA/ASA/BUT: 31.4 pg/mg mucosa/h, P < 0.01 versus DCA: 56.9 pg/mg mucosa/h). Butyrate and aspirin showed no synergistic effects. The results indicate a normalization of DCA-induced hyperproliferation of colonic mucosa by butyrate, and, even more efficiently, by aspirin. The data support the hypothesis that butyrate and aspirin can act as chemopreventive agents in colon carcinogenesis.
Gostner
A
A
Department of Medicine, University of Würzburg, Gastrolabor, Germany.
Dusel
G
G
Kelber
E
E
Scheppach
W
W
Bartram
H P
HP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000494:pharmacology*; D001707:Biopsy, Needle; D002087:Butyrates / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D003113:Colonoscopy; D046508:Culture Techniques; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011336:Probability; D012016:Reference Values; D018709:Statistics, Nonparametric
D002087:Butyrates; D015232:Dinoprostone; D001241:Aspirin