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Indole-3-Carbinol Shown To Induce Programmed Cell Death in Breast Cancer Cells, But Not Normal Breast Epithelial Cells

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Breast cancer is the most common cancer in women in the United States, and remains the second leading cause of cancer-related female deaths in the U.S. The current treatment for breast cancer involves options such as surgery, chemotherapy, and radiation, or a combination thereof. Although the majority of patients with metastatic breast cancer will experience an initial improvement, long-term survival is only modestly improved with contemporary therapies. As a result other interventions aimed at preventing this disease and treating it more effectively have been the focus of much effort, and emphasis on nutrition and supplementation are most noteworthy in this regard. Most recently a study by KMW Rahman, O Aranha, and FH Sarkar, published in Nutrition and Cancer, revealed that exposure of various human breast cancer cell lines to indole-3-carbinol induced programmed cell death (apoptosis) of these highly malignant cells.

            There is considerable dietary and epidemiological evidence suggesting the protective effect of fruits and vegetables against cancer of the liver, colon, stomach, lung, and breast. These foods are known to contain many phytochemicals, particularly indole-3-carbinol. Cruciferous vegetables (broccoli, cauliflower, cabbage, Brussels sprouts, bok choy) are an extremely rich source of this important nutrient. It has been shown that indole-3-carbinol and its metabolites possess anti-carcinogenic effects in experimental animals and inhibit the growth of various human cancer cells.

            In term of breast cancer, indole-3-carbinol has been shown to suppress the growth of both estrogen-dependent and estrogen-independent human breast cancer cell lines, suggesting that in addition to acting as a phytoestrogen (which binds to estrogen receptors on estrogen-dependent breast cancer cells), it also exerts other influences on breast cancer cells that block their ability to replicate. These anti-proliferative mechanisms are presently the subject of intensive investigation.

            In the most recent study of this subject by KMW Rahman, et al, the researchers were able to show that indole-3-carbinol not only suppressed the cell division of certain breast cancer cell lines, but that it further served to induce programmed cell death (apoptosis) of these malignant cell while producing no such effect on normal breast cells. Simply stated, indole-3-carbinol demonstrates an ability to selectively encourage breast cancer cells to commit suicide while allowing normal breast epithelial cells to thrive in a normal fashion. This effect may be one of the reasons that a high lifetime intake of cruciferous vegetables is associated with a significant reduction in breast cancer, according to epidemiological studies. Moreover, these findings suggest that women with breast cancer may be well advised to consume cruciferous vegetables and possibly supplement their diet with indole-3-carbinol supplements. In the words of the researchers, “indole-3-carbinol may have a wide therapeutic application because of its selective apoptosis-inducing activity against cancer cells without inducing apoptosis of non-tumorigenic breast epithelial cells”.

            As for the mechanism through which indole-3-carbinol produces programmed cell death of breast cancer cells, this recent study demonstrated that indole-3-carbinol induces Bax translocation to the mitochondria, causing mitochondrial depolarization, resulting in the loss of mitochondrial potential, leading to the release of cytochrome c and subsequent cell death in certain breast cancer cell lines, but not in others. Bax is a gene that is one of several associated with cancer development. During apoptosis, Bax has been shown in previous studies to translocate from the cytosol of the cell to the mitochondria. Bax is a 21-kDa pro-apoptotic protein, localized in the mitochondria, which regulates programmed cell death. Bax was reported to be a cytosolic protein in healthy living cells, and upon induction of apoptosis, it translocates to the mitochondria. This translocation is rapid and occurs at an early stage of translocation.

            The discovery that certain natural agents (isoflavones from soy beans, Vitamin E succinate, indole-3-carbinol etc) can induce apoptosis of various human cancer cell lines, has fostered research aimed at the development of cancer drugs that can provide the same kind of selective ability to encourage cancer cells to commit suicide, but with even more powerful ability. In the meantime, it remains more prudent than ever before to recommend the daily consumption of indole-3-carbinol sources to your patients and to consider boosting indole-3-carbinol consumption in patients with certain cancers, as part of the complementary management of these cases.

 

Reference:

Rahman KMW, Aranha O, and Sarkar FH. Indole-3-carbinol (I3C) induces apoptosis in tumorigenic but not in nontumorigenic breast epithelial cells. Nutrition and Cancer 2003;45(1):101-112

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