Sulindac, 3,3'-diindolylmethane and curcumin reduce carcinogenesis in the Pirc rat, an Apc-driven model of colon carcinogenesis.

BACKGROUND: Recently, we showed that Sulindac (SU; 320 ppm) reduces precancerous lesions in the colon of Pirc rats, mutated in the Apc gene. Surprisingly, previous data in Apc-mutated mice showed that SU, with reported efficacy in Familial Adenomatous Polyposis (FAP), increases colon carcinogenesis. Therefore, we assessed the effect of SU 320 ppm in a long-term carcinogenesis experiment in Pirc rats. Moreover, since side effects of SU hamper its chronic use and a combination of drugs could be more effective and less toxic than single agents, we also studied whether two natural compounds, 3,3'-diindolylmethane (DIM; 250 ppm) and curcumin (CUR; 2000 ppm), with or without lower doses of SU could affect carcinogenesis METHODS: Pirc rats were fed an AIN76 diet containing SU, DIM and CUR and sacrificed at 8 months of age to measure intestinal tumours. Apoptosis and proliferation in the normal colon mucosa, as well as gene expression profile were studied RESULTS: Colon tumours were significantly reduced by SU 320 ppm (62 % reduction over Controls), by DIM and CUR without or with SU 80 and 160 ppm (50, 53 and 58 % reduction, respectively) but not by SU 80 ppm alone. Total tumours (colon and small intestine) were reduced by SU (80 and 320 ppm) and by DIM and CUR. Apoptosis in the normal mucosa was significantly increased by SU 320 ppm, and slightly increased by DIM and CUR with or without SU. A slight reduction in Survivin-Birc5 expression was observed with all the treatments compared to Controls. Proliferative activity was not varied CONCLUSIONS: The results on SU reinforce the validity of Pirc rats to identify chemopreventive products. Moreover, the efficacy of the DIM and CUR combination to lower colon tumours, suggests an alternative strategy to be exploited in patients at risk.

No effects of olive oils with different phenolic content compared to corn oil on 1,2-dimethylhydrazine-induced colon carcinogenesis in rats.

BACKGROUND: Some epidemiological and experimental studies suggest that olive oil, despite its elevated caloric content, may have protective activity against colon cancer, partially due to its phenolic content. However, little experimental evidence exists to support this claim in vivo. AIM OF THE STUDY: To test the effect of olive oils with different phenolic content in a well-characterized model of colon carcinogenesis, comparing them with corn oil (CO). METHODS: F344 rats were fed AIN-76 based diets for the entire experimental period; the diets contained 23% (w/w) of lipids from three different sources: extra-virgin olive oil rich in phenolic compounds (EV), rectified olive oil (ROO) with the same fatty acid composition but devoid of phenolic compounds and CO as a control diet. One week later, rats were induced with 1,2-dimethylhydrazine (DMH) (150 mg/kg b.w. x 2 times) to measure preneoplastic lesions (aberrant crypt foci (ACF) and mucin depleted foci (MDF)) and tumours in the intestine. RESULTS: Thirteen weeks after DMH, the numbers of ACF and MDF were similar in the different groups (ACF/colon were 344.9 +/- 27.0, 288.6 +/- 28.5 and 289.8 +/- 21.4 in CO, EV and ROO groups, respectively, means +/- SE; MDF/colon were 8.83 +/- 1.2, 8.41 +/- 1.5 and 8.75 +/- 1.6 in CO, EV and ROO groups, respectively, means +/- SE). Thirty-two weeks after DMH, the incidence of tumours (rats with tumours/rats in the group) did not differ among the different groups (20/21, 18/19 and 20/20 in the CO, EV, and ROO groups, respectively). Similarly, the number of tumours/ rat in the colorectum (both adenomas and cancers) was not different in the three different groups (2.33 +/- 0.26, 2.42 +/- 0.41 and 2.25 +/- 0.40 in CO, EV and ROO groups, respectively, means +/- SE). CONCLUSIONS: Olive oil, irrespective of its phenolic content, does not affect DMH-induced colon carcinogenesis in F344 rats compared with CO.