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Protective effect of indole-3-carbinol on breast cancer.

Recent results from epidemiology, in vitro cell culture and in vivo studies have suggested the benefits of indole-3-carbinol for the prevention of many types of cancer, including breast cancer. Oral administration of indole-3-carbinol has been shown to influence our estrogen metabolism in humans in a beneficial manner. It increases the ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone. Experimental and clinical evidence suggests that 16alpha-hydroxylated estrogen metabolites react as strong estrogens, and are associated with breast cancer risk, while 2-hydroxylated metabolites have a lower estrogenic activity and are weakly related to this disease. Indole-3-carbinol is a good candidate for clinical trial in women at increased risk of developing breast cancer. Fan S and co-workers of the Georgetown University (New York) reported that both indole-3-carrbinol and genistein target the breast cancer susceptibility genes in both prostate and breast cancer cells [4]. The breast cancer susceptibility genes are responsible for the suppression of tumor growth, not only of breast cancer cells but also ovarian and prostate cancer cells. This in-vitro study showed that the phytochemicals induced the expression of these genes.

An in-vitro study with cultured human breast cancer cells demonstrated that indole-3-carbinol directly inhibited elastase enzymatic activity and concluded that this phytochemicals, or similar compounds, should be further investigated as drug for the treatment of human breast cancers where high elastase levels are correlated with poor prognosis [2]. More specifically they found that indole-3-carbinol shifted the stable accumulation of cyclin E protein from the lower molecular mass form, that is associated with cancer cell proliferation and poor clinical outcomes, to its higher molecular mass form, that is typically produced in normal cells. A Taiwanese study found that indole-3-carbinol reduced the invasion and migration of breast cancer cells [3]. The phytochemical inhibited matrix metalloproteinases expression by blocking the ERK/Sp1-mediated gene transcription.

Indole-3-carbinol might improve the effect of tamoxifen according to an experiment with rats carried out by the University of Minnesota [4]. Tamoxifen is a selective estrogen receptor modulator that is used in the treatment of breast cancer. The scientists induced tumors in rats by dosing the carcinogen dimethylbenz-a-anthracene and then treated the rats with tamoxifen, indole-3-carbionol or a combination of both. All three types of treatment resulted in a significant increased latency and decreased mass of malignant mammary tumors, but also treatment with indole-3-carbinol, although the effect of indole-3-carbinol alone was weaker.

A study by scientists of the University of California concluded that indole-32-carbinol had an influence on the function and expression of estrogen receptor-alpha (ERA) and estrogen receptor-beta (ERB) [6]. By increasing the ratio of ERA to ERB indole-3-carbinol could reduce the proliferation of human breast cancer cells. The tests were conducted on breast cancer cells that expressed both ERA and ERB. Treatment of these breast cancer cells with indole-3-carbinol strongly inhibited ERB protein production, without that of ERA.

Indole-3-carbinol selectively induced apoptosis in breast cancer cells, but not in nontumorigenic breast cells, suggesting the potential therapeutic benefit of I3C against breast cancer [7]. Low levels of indole-3-carbinol inhibited the growth of the tumor cells more than that of normal breast cells. The phytochemical upregulated Bax/Bcl-2 ratio and downregulated Bcl-xL expression only in the breast cancer cells.

[1] Prevention and treatment of cancer with indole-3-carbinol. Altern Med Rev. 2001 Dec;6(6):580-9.
[2] The dietary phytochemical indole-3-carbinol is a natural elastase enzymatic inhibitor that disrupts cyclin E protein processing. Proc Natl Acad Sci U S A. 2008 Dec 8.
[3] Indole-3-carbinol Inhibits Sp1-Induced Matrix Metalloproteinase-2 Expression To Attenuate Migration and Invasion of Breast Cancer Cells. J Agric Food Chem. 2008 Dec 5.
[4] BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and genistein in breast and prostate cancer cells. Br J Cancer. 2006 Feb 13;94(3):407-26.
[5] Suppression of mammary gland carcinogenesis by post-initiation treatment of rats with tamoxifen or indole-3-carbinol or their combination. Eur J Cancer Prev. 2007 Apr;16(2):130-41.
[6] Indole-3-carbinol selectively uncouples expression and activity of estrogen receptor subtypes in human breast cancer cells. Mol Endocrinol. 2006 Dec;20(12):3070-82. Epub 2006 Aug 10.
[7] Indole-3-carbinol (I3C) induces apoptosis in tumorigenic but not in nontumorigenic breast epithelial cells. Nutr Cancer. 2003;45(1):101-12.

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