QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Auborn, K. J. Articles by Carter, T. H. Search for Related Content PubMed PubMed Citation Articles by Auborn, K. J. Articles by Carter, T. H.

---

Supplement: Nutritional Genomics and Proteomics in Cancer Prevention

Indole-3-Carbinol Is a Negative Regulator of Estrogen^{1 ,2}

Karen J. Auborn^*,,**,3, Saijun Fan^*,, Eliot M. Rosen^*,,, Leslie Goodwin^*, Alamelu Chandraskaren^*, David E. Williams^,#, DaZhi Chen^* and Timothy H. Carter^*,,

^* North Shore–Long Island Jewish Research Institute, Manhasset, NY 11030, Departments of Otolaryngology and Radiology, Long Island Jewish Medical Center, Long Island Campus of Albert Einstein College of Medicine, New Hyde Park, NY 11040, Departments of ^** Microbiology and Immunology and Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, Department of Environmental and Molecular Toxicology and ^# Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 and Department of Biological Sciences, St. Johns University, Jamaica, NY 11530

³ To whom correspondence should be addressed. E-mail: kauborn{at}nshs.edu.

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)-. 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-. 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-. 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.

KEY WORDS: • indole-3-carbinol • diindolylmethane • genistein • estradiol

This article has been cited by other articles:

				S. Smith, D. Sepkovic, H. L. Bradlow, and K. J. Auborn 3,3'-Diindolylmethane and Genistein Decrease the Adverse Effects of Estrogen in LNCaP and PC-3 Prostate Cancer Cells J. Nutr., December 1, 2008; 138(12): 2379 - 2385. [Abstract] [Full Text] [PDF]

				S. C. Tilton, J. D. Hendricks, G. A. Orner, C. B. Pereira, G. S. Bailey, and D. E. Williams Gene expression analysis during tumor enhancement by the dietary phytochemical, 3,3'-diindolylmethane, in rainbow trout Carcinogenesis, July 1, 2007; 28(7): 1589 - 1598. [Abstract] [Full Text] [PDF]

				E. T. Chang, V. S. Lee, A. J. Canchola, C. A. Clarke, D. M. Purdie, P. Reynolds, H. Anton-Culver, L. Bernstein, D. Deapen, D. Peel, et al. Diet and Risk of Ovarian Cancer in the California Teachers Study Cohort Am. J. Epidemiol., April 1, 2007; 165(7): 802 - 813. [Abstract] [Full Text] [PDF]

				K. J. Auborn Can Indole-3-Carbinol-Induced Changes in Cervical Intraepithelial Neoplasia Be Extrapolated to Other Food Components? J. Nutr., October 1, 2006; 136(10): 2676S - 2678S. [Full Text] [PDF]

				J. A. Savino III, J. F. Evans, D. Rabinowitz, K. J. Auborn, and T. H. Carter Multiple, disparate roles for calcium signaling in apoptosis of human prostate and cervical cancer cells exposed to diindolylmethane. Mol. Cancer Ther., March 1, 2006; 5(3): 556 - 563. [Abstract] [Full Text] [PDF]