phytochemicals Phytochemicals

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Anti-cancer effect of indole-3-carbinol

Diets high in vegetables, especially cruciferous vegetables provide protection against cancer. Cruciferous vegetables provide the only source of glucosinolates, which breaks down in indole-3-carbinol and sulforaphane. The anticancer effects of indole-3-carbinol and diindoylmethane are the result of specific activities: inducing phase I and phase II enzymes that metabolize carcinogens, enhancing DNA repair, inducing G1 cell cycle arrest and apoptosis. Most studies have focused on the effects on endometrial cancer, breast cancer and prostate cancer.

Tumor progression relies on the upregulation of signaling pathways relevant to cell proliferation and increased resistance against chemotherapeutic agents. Indole-3-carbinol and its metabolite diindoylmethane target different aspects of carcinogenesis, such as estrogen metabolism, estrogen receptor signaling, Akt-NF kappa B signaling, caspase activation, cyclin-dependent kinase activities, endoplasmic reticulum stress, and expression of tumor suppression genes [1]. Many in-vitro results have demonstrated the anticancer effect of indol-3-carbinol, but these favorable results should be treated with extra care because of its low biological availability in humans. A phase I trial demonstrated that after a oral intake of up to 1200 mg indol-3-carbionol did not result in detectable plasma levels of the phytochemical [2]. The researchers could only detect diindolylmethane , a metabolite of indole-3-carbinol, which reached max plasma level 2 hours after the administration on indole-63-carbinol, but disappeared almost completely after 12 hours. The pharmaceutical industry has already developed and patented anti-cancer chemicals with structure similar to that of diindolyl)methane, a metabolite of indole-3-carbinol.

[1] Indole-3-carbinol as a chemopreventive and anti-cancer agent. Cancer Lett. 2008 Apr 18;262(2):153-63.
[2] Single-dose and multiple-dose administration of indole-3-carbinol to women: pharmacokinetics based on 3,3'-diindolylmethane. Cancer Epidemiol Biomarkers Prev. 2006 Dec;15(12):2477-81.
[3] The natural chemopreventive compound indole-3-carbinol: state of the science. In Vivo. 2006 Mar-Apr;20(2):221-8.

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