This Article Full Text Full Text (PDF) 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 Kijima, I. Articles by Chen, S. Search for Related Content PubMed PubMed Citation Articles by Kijima, I. Articles by Chen, S.

Grape Seed Extract Is an Aromatase Inhibitor and a Suppressor of Aromatase Expression

Department of Surgical Research, Beckman Research Institute of the City of Hope, Duarte, California

Requests for reprints: Shiuan Chen, Department of Surgical Research, Beckman Research Institute of the City of Hope, 1500 E. Duarte Road, Duarte, CA 91010. Phone: 626-359-8111, ext. 63454; Fax: 626-301-8972; E-mail: schen{at}coh.org.

Aromatase is the enzyme that converts androgen to estrogen. It is expressed at higher levels in breast cancer tissues than normal breast tissues. Grape seed extract (GSE) contains high levels of procyanidin dimers that have been shown in our laboratory to be potent inhibitors of aromatase. In this study, GSE was found to inhibit aromatase activity in a dose-dependent manner and reduce androgen-dependent tumor growth in an aromatase-transfected MCF-7 (MCF-7aro) breast cancer xenograft model, agreeing with our previous findings.

We have also examined the effect of GSE on aromatase expression. Reverse transcription-PCR experiments showed that treatment with 60 µg/mL of GSE suppressed the levels of exon I.3–, exon PII–, and exon I.6–containing aromatase mRNAs in MCF-7 and SK-BR-3 cells. The levels of exon I.1–containing mRNA, however, did not change with GSE treatment. Transient transfection experiments with luciferase-aromatase promoter I.3/II or I.4 reporter vectors showed the suppression of the promoter activity in a dose-dependent manner. The GSE treatment also led to the down-regulation of two transcription factors, cyclic AMP-responsive element binding protein-1 (CREB-1) and glucocorticoid receptor (GR). CREB-1 and GR are known to up-regulate aromatase gene expression through promoters I.3/II and I.4, respectively. We believe that these results are exciting in that they show GSE to be potentially useful in the prevention/treatment of hormone-dependent breast cancer through the inhibition of aromatase activity as well as its expression. (Cancer Res 2006; 66(11): 5960-7)

This article has been cited by other articles:

				J. Lu, K. Zhang, S. Chen, and W. Wen Grape seed extract inhibits VEGF expression via reducing HIF-1{alpha} protein expression Carcinogenesis, April 1, 2009; 30(4): 636 - 644. [Abstract] [Full Text] [PDF]

				W. Wen, J. Lu, K. Zhang, and S. Chen Grape Seed Extract Inhibits Angiogenesis via Suppression of the Vascular Endothelial Growth Factor Receptor Signaling Pathway Cancer Prevention Research, December 1, 2008; 1(7): 554 - 561. [Abstract] [Full Text] [PDF]

				K. Chatelain, S. Phippen, J. McCabe, C. A. Teeters, S. O'Malley, and K. Kingsley Cranberry and Grape Seed Extracts Inhibit the Proliferative Phenotype of Oral Squamous Cell Carcinomas Evid. Based Complement. Altern. Med., July 23, 2008; (2008) nen047v1. [Abstract] [Full Text] [PDF]

				I. Kijima, J. Ye, C. Glackin, and S. Chen CCAAT/Enhancer Binding Protein {delta} Up-regulates Aromatase Promoters I.3/II in Breast Cancer Epithelial Cells Cancer Res., June 1, 2008; 68(11): 4455 - 4464. [Abstract] [Full Text] [PDF]

				H. K. Choi, S. H. Roh, H. G. Kim, E. H. Han, H. G. Jeong, and K. W. Kang Enhanced expression of aromatase in p53-inactivated mammary epithelial cells Endocr. Relat. Cancer, March 1, 2008; 15(1): 139 - 147. [Abstract] [Full Text] [PDF]