Fructooligosaccharide associated with celecoxib reduces the number of aberrant crypt foci in the colon of rats

Abstract

-According to Burkitt's hypothesis, dietary fibres may protect against the development of colorectal cancer. In rats, studies have shown that only butyrate-producing fibres are protective. In parallel, in humans, non-steroidal anti-inflammatory drugs, which target cyclooxygenases, have been shown to display a protective effect against colorectal cancer. Among them, COX-2-selective inhibitors which present less side effects than non-selective agents, are promising as chemopreventive agents. Our aim was to analyse the effect of an association between butyrate-producing fibres and the COX-2 inhibitor on the development of aberrant crypt foci (ACF) in rats. Fisher F344 rats were fed with (1) a standard low fibre control diet; (2) the standard diet supplemented with 1500 ppm celecoxib; (3) a diet supplemented with 6% fructo-oligosaccharide (FOS); and (4) a diet with both celecoxib and FOS. Three weeks later, the rats were injected twice with azoxymethane and the number of ACF was determined 15 weeks later. In the control group, 43.8 ± 6.4 ACF were found. This number was not significantly modified by the addition of FOS or celecoxib alone to the diet. However, the association of FOS and celecoxib resulted in a 61% reduction in the number of ACF (P < 0.01). The number of aberrant crypt per foci was also reduced. Thus, although no significant effect of celecoxib or FOS alone was identified, the association of butyrate-producing fibre and celecoxib was effective in preventing the development of ACF. This preliminary study argues for a strong protective effect of such an association which deserves further studies. COX-2 / butyrate / colorectal cancer / NSAID

Celecoxib Treatment Alters the Gene Expression Profile of Normal Colonic Mucosa

“…ACFs are considered to be an early preneoplastic lesion in the colon (75), and the ability to decrease the frequency of ACF after carcinogen treatment is used routinely in experimental models of colon cancer to estimate the cancer preventive effect of different agents (76). It is particularly well established that NSAIDs (77)(78)(79) and celecoxib (80)(81)(82)(83) decrease the frequency of carcinogen-induced ACFs in the colon in animal models. It has also been shown that the number of ACF in patients who received sulindac sulfide is decreased (84).…”

Gene Expression Patterns Distinguish Colonoscopically Isolated Human Aberrant Crypt Foci from Normal Colonic Mucosa

“…It is known that nonsteroidal anti-inflammatory drugs, and particularly celecoxib, decrease the frequency of ACF in humans as well as in rodent models of carcinogen-induced colon cancer (67)(68)(69)(70). We compared the changes in gene expression found in normal descending colonic mucosa of patients treated with celecoxib for 1 year (71) to the differences seen in gene expression between ACF and NM from the descending colon.…”

Dietary Cancer Chemopreventive Agents – Targeting Inflammation and Nrf2 Signaling Pathway

“…CUR was also reported to inhibit AOM-induced rat colon carcinogenesis by suppression of prostaglandin (PG) and thromboxane (Tx) formation [75]. Similar to isothiocyanates, CUR is a strong activator of Nrf2mediated transcription of ARE-luciferase reporter gene, as well ↓ mean tumor volume in all treatment group; inhibitory effect significantly stronger in combination of α-TEA + celecoxib (1 250) group than single compound/drug [85] Fructo-oligosaccharide (6 %), celecoxib 1 500 ppm AOM-induced aberrant crypt foci (ACF) in rat ↓ 61 % in combination; no effect with celecoxib alone [86] Anthocyanin-rich tart cherry extract (375, 750, 1 500, 3 000 mg/kg diet), sulindac (100 mg/kg diet)…”