Resveratrol, a phytoalexin found in grapes and other food products, was purified and shown to have cancer chemopreventive activity in assays representing three major stages of carcinogenesis. Resveratrol was found to act as an antioxidant and antimutagen and to induce phase II drug-metabolizing enzymes (anti-initiation activity); it mediated anti-inflammatory effects and inhibited cyclooxygenase and hydroperoxidase functions (antipromotion activity); and it induced human promyelocytic leukemia cell differentiation (antiprogression activity). In addition, it inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. These data suggest that resveratrol, a common constituent of the human diet, merits investigation as a potential cancer chemopreventive agent in humans.

https://science.sciencemag.org/content/sci/275/5297/218.full.pdf

Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes

The biochemistry and medical significance of the flavonoids.

Bile salt biotransformations by human intestinal bacteria.

[Crohn's disease].

Background and Methods. Experiments in animals and two epidemiologic studies in humans suggest that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) may be protective against colon cancer. We tested this hypothesis in a prospective mortality study of 662,424 adults who provided information in 1982 on the frequency and duration of their aspirin use. Death rates from colon cancer were measured through 1988. The possible influence of other risk factors for colon cancer was examined in multivariate analyses for 598 case patients and 3058 matched control subjects drawn from the cohort. Results. Death rates from colon cancer decreased with more frequent aspirin use in both men and women. The relative risk among persons who used aspirin 16 or more times per month for at least one year was 0.60 in men (95 percent confidence interval, 0.40 to 0.89) and 0.58 in women (95 percent confidence interval, 0.37 to 0.90). The risk estimates were unaffected when we excluded persons who reported at ent...

https://www.nejm.org/doi/pdf/10.1056/NEJM199112053252301

Aspirin use and reduced risk of fatal colon cancer

Promoting Effect of Bile Acids on Colon Carcinogenesis After Intrarectal Instillation of N-Methyl-N′ nitro-N-nitrosoguanidine in Rats

Inhibitory effects of natural carotenoids, α-carotene, β-carotene, lycopene and lutein, on colonic aberrant crypt foci formation in rats

Various natural carotenoids were proven to have anticarcinogenic activity. Epidemiological investigations have shown that cancer risk is inversely related to the consumption of green and yellow vegetables and fruits. Since β-carotene is present in abundance in these vegetables and fruits, it has been investigated extensively as possible cancer preventive agent. However, various carotenoids which co-exist with β-carotene in vegetables and fruits also have anti-carcinogenic activity. And some of them, such as α-carotene, showed higher potency than β-carotene to suppress experimental carcinogenesis. Thus, we have carried out more extensive studies on cancer preventive activities of natural carotenoids in foods; i.e., lutein, lycopene, zeaxanthin and β-cryptoxanthin. Analysis of the action mechanism of these natural carotenoids is now in progress, and some interesting results have already obtained; for example, β-cryptoxanthin was suggested to stimulate the expression of RB gene, an anti-oncogene, and p73 gene, which is known as one of the p53-related genes. Based on these results, multi-carotenoids (mixture of natural carotenoids) seems to be of interest to evaluate its usefulness for practice in human cancer prevention.

Cancer prevention by natural carotenoids

The effect of intestinal microflora on the sensitivity of the colon to the carcinogenic effect of 1,2-dimethylhydrazine (DMH), which needs metabolic activation, and N -methyl- N ′-nitro- N -nitrosoguanidine a direct-acting carcinogen, was studied using Fischer germ-free and conventional female rats. None of the germ-free rats that received s.c. injections of DMH, 10 mg/week/kg body weight for 20 weeks and autopsied after the last injection showed colon tumors, whereas 17% of the conventional rats treated similarly developed adenocarcinomas of the colon. At 20 weeks after the last injection of DMH, 11% of germ-free rats developed adenomas, whereas 25% of the conventional rats showed colonic tumors, 67% of which were adenocarcinomas and 34% of which were adenomas. In contrast to DMH, i.r. injection of N -methyl- N ′-nitro- N -nitrosoguanidine (total dose, 48 mg in 20 weeks) nearly doubled the multiple colonic tumors in germ-free rats compared to conventional controls. It is concluded that the intestinal microflora play a modifying role in colon carcinogenesis by DMH.

https://cancerres.aacrjournals.org/content/canres/34/9/2368.full.pdf

Colon carcinogenesis in germ-free rats with 1,2-dimethylhydrazine and N-methyl-n'-nitro-N-nitrosoguanidine.

The effect of treatment with indomethacin on methylazoxymethanol-induced rat large bowel carcinomas was investigated. Eight-week-old male Donryu rats received an intraperitoneal injection of 20 mg/kg body weight of methylazoxymethanol acetate once a week for 6 weeks. Fifteen rats were sacrificed at the 25th week. It was confirmed that the incidence of large bowel tumors (adenocarcinomas) was 60% and the mean number of tumors per tumor-bearing rat was 2.0. The other rats (23 approximately 30 rats in each group) were given the treatment with an intrarectal instillation of 7.5 mg/kg body weight of indomethacin, 7.5 mg/kg of hydrocortisone, 75 mg/kg of PS-K, vehicle alone, or non-treatment daily from the 27th to 29th week. All of these rats were sacrificed at the 30th week. The tumor incidence was 50% or 55% in indomethacin- or hydrocortisone-treated rats. It was significantly lower than 83% or 87% of the rats treated wih PS-K or vehicle, or untreated. The mean number of tumors was also smaller in those 2 groups of rats (2.0 or 2.1 tumors) than in 3 groups (3.5 or 3.3 tumors). The results demonstrated that the intrarectal dose of indomethacin and hydrocortisone inhibited the development of tumors from microscopic carcinoma lesions in the large bowel and growing further. It seems that indomethacin might be effective to treat the early stage disease with relatively small number of growing tumor cells.

Tomio Narisawa

Papers

Promoting Effect of Bile Acids on Colon Carcinogenesis After Intrarectal Instillation of N-Methyl-N′ nitro-N-nitrosoguanidine in Rats

Inhibitory effects of natural carotenoids, α-carotene, β-carotene, lycopene and lutein, on colonic aberrant crypt foci formation in rats

Cancer prevention by natural carotenoids

Colon carcinogenesis in germ-free rats with 1,2-dimethylhydrazine and N-methyl-n'-nitro-N-nitrosoguanidine.

Antitumor activity of indomethacin on methylazoxymethanol-induced large bowel tumors in rats.