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Chemopreventive effect of the phytochemical indole-3-carbinol

Many studies with rodents show that indole-3-carbinol has chemopreventive actions by inducting phase I and phase II enzymes, inhibition of proliferation and induction of apoptosis in tumor cells [2]. The study published in the Journal of Nutrtion concluded that high concentrations of the phytochemicals crambene and indole-3-carbinol showed chemoprotection by reducing the initiation of carcinogenesis by aflatoxin B1, but that low concentrations, which correspond to realistic consumption, showed no effects. One human study showed that the daily administration of indole-3-carbinol increased levels of glutathione-S-transferase and P450 1A2 and increased the ratio of 2-:16-hydroxyestrone without causing any toxic effects [3]. Scientists from the University of Minnesota found that indole-3-carbinol, a phytochemical found in broccoli and other cruciferous vegetables, may protect against lung cancer, according their an in-vivo study on mice [1]. They found that mice fed with varying doses of indole-3-carbinol dose-dependently showed a reduced the number of lung tumors induced by carcinogens found in tobacco smoke. The lung cancers were induced by a mixture of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo(a)pyrene (these two chemicals are the most potent tobacco smoke carcinogens in rodent models and are strongly implicated in the etiology of lung cancer in smokers), after which they were fed on diets with different doses indole-3-carbinol, ranging from 1 to 112 μmol/g. When the indole-3-carbinol was administered during the treatment with carcinogens the number of lung tumors were reduced in a dose-dependent manner up to 88%. Also the administration of indole-3-carbinol 1 week after exposure to the carcinogen significantly reduced the number of lung cancers as much as 74% for the highest dose of the phytochemical. The study concluded that indole-3-carbinal is clearly efficient in the prevention of tobacco carcinogen–induced lung tumorigenesis in experimental mice. This mouse model of lung tumorigenesis is well suited for the identification of chemopreventive agents but additional human studies are required to evaluate this phytochemical as a chemopreventive agent for smokers.

A study conducted at Seoul National University investigated the chemopreventive effect of indol-3-carbinol on rat liver epithelial cells treated with hydrogen peroxide [4]. The researchers found that indole-3-carbinol prevented the inhibition of gap junctional intercellular communication induced by hydrogen peroxide. Poor gap junctional intercellular communication accelerates the progression of carcinogenesis. A Japanese in-vivo study concluded that a treatment of prepubertal female rats with indole-3-carbinol protected against mammary carcinogenesis, induced by the carcinogen N-methyl-N-nitrosourea [5]. They found that indole-3-carbinol reduced mammary carcinoma incidence and prolonged latency.

[1] Dose-Dependent Inhibition of Tobacco Smoke Carcinogen–Induced Lung Tumorigenesis in A/J Mice by Indole-3-Carbinol. Cancer Prevention Research 1, 568-576, December 1, 2008.
[2] Cruciferous vegetables, isothiocyanates and indoles. Vol. 9. Lyon: IARC Printing Press; 2004. p. 171–76.
[3] A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol Biomark Prev 2005;14:1953–60.
[4] Indole-3-carbinol prevents H(2)O(2)-induced inhibition of gap junctional intercellular communication by inactivation of PKB/Akt. J Vet Med Sci. 2008 Oct;70(10):1057-63.
[5] Effects of prepubertal indole-3-carbinol treatment on development of N-methyl-N-nitrosourea-induced mammary carcinomas in female Sprague-Dawley rats.In Vivo. 2007 Nov-Dec;21(6):983-8. Effects of prepubertal indole-3-carbinol treatment on development of N-methyl-N-nitrosourea-induced mammary carcinomas in female Sprague-Dawley rats.

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