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Indole-3-carbinol is a negative regulator of estrogen
Karen J Auborn1, Saijun Fan, Eliot M Rosen
1North Shore-Long Island Jewish Research Institute, Manhasset, NY 11030, USA. kauborn@nshs.edu
Abstract:
Studies increasingly indicate that dietary indole-3-carbinol (I3C) prevents the development of estrogen-enhanced cancers including breast, endometrial and cervical cancers. Epidemiological, laboratory, animal and translational studies support the efficacy of I3C. Whereas estrogen increases the growth and survival of tumors, I3C causes growth arrest and increased apoptosis and ameliorates the effects of estrogen. Our long-range goal is to best use I3C together with other nutrients to achieve maximum benefits for cancer prevention. This study examines the possibility that induction of growth arrest in response to DNA damage (GADD) in genes by diindolylmethane (DIM), which is the acid-catalyzed condensation product of I3C, promotes metabolically stressed cancer cells to undergo apoptosis. We evaluated whether genistein, which is the major isoflavonoid in soy, would alter the ability of I3C/DIM to cause apoptosis and decrease expression driven by the estrogen receptor (ER)-alpha. Expression of GADD was evaluated by real-time reverse transcription-polymerase chain reaction. Proliferation and apoptosis were measured by a mitochondrial function assay and by fluorescence-activated cell sorting analysis. The luciferase reporter assay was used to specifically evaluate expression driven by ER-alpha. The estrogen-sensitive MCF-7 breast cancer cell line was used for these studies. We show a synergistic effect of I3C and genistein for induction of GADD expression, thus increasing apoptosis, and for decrease of expression driven by ER-alpha. Because of the synergistic effect of I3C and genistein, the potential exists for prophylactic or therapeutic efficacy of lower concentrations of each phytochemical when used in combination.
Insights
Dietary indole-3-carbinol (I3C) and genistein show a synergistic effect in preventing estrogen-driven cancers. Combining these compounds enhances apoptosis and reduces estrogen receptor activity, offering potential for cancer prevention.
Area of Science:
- Oncology
- Nutritional Biochemistry
- Molecular Biology
Background:
- Dietary indole-3-carbinol (I3C) and its metabolite diindolylmethane (DIM) show promise in preventing estrogen-sensitive cancers.
- Estrogen promotes tumor growth, while I3C induces growth arrest and apoptosis.
- Genistein, a soy isoflavonoid, is investigated for its potential to enhance I3C/DIM's anti-cancer effects.
Purpose of the Study:
- To investigate the synergistic effects of I3C and genistein on apoptosis induction in cancer cells.
- To determine if genistein modulates the ability of I3C/DIM to decrease estrogen receptor (ER)-alpha activity.
- To explore the role of Growth Arrest and DNA Damage (GADD) genes in the combined phytochemical effect.
Main Methods:
- Utilized the estrogen-sensitive MCF-7 breast cancer cell line.
- Assessed GADD gene expression via real-time reverse transcription-polymerase chain reaction.
- Measured cell proliferation and apoptosis using mitochondrial function assays and fluorescence-activated cell sorting.
- Evaluated ER-alpha activity using a luciferase reporter assay.
Main Results:
- A synergistic effect was observed between I3C and genistein in inducing GADD gene expression.
- The combination of I3C and genistein significantly increased cancer cell apoptosis.
- Combined treatment led to a decrease in expression driven by ER-alpha.
- Synergistic effects were noted at lower concentrations of each phytochemical.
Conclusions:
- The combination of I3C and genistein exhibits a synergistic effect in promoting apoptosis and reducing ER-alpha activity.
- This synergistic interaction suggests potential for using lower concentrations of these phytochemicals for cancer prevention.
- Further research into combined phytochemical strategies holds promise for both prophylactic and therapeutic applications in cancer treatment.