Modulation of Growth and Differentiation in Breast Cancer by Soy Isoflavones
Abstract
Our studies investigate the in vivo effects of soy isoflavones on human breast tissues obtained from lumpectomy/mastectomy specimens. We investigate the effect of increased tissue concentration of isoflavones for a period of three weeks on breast cancer proliferation, differentiation and cell cycle regulatory proteins. Patients with ductal carcinoma in situ (DCIS) or invasive breast cancer are randomly assigned to take 100 mg soy isoflavone (Novasoy-Trademark, Archer Daniels Midland Company, Decatur, Illinois) or placebo daily for three weeks prior to surgery. Plasma isoflavone levels are measured at baseline and after three weeks in both groups. Tissue specimens by immunohistochemistry and Western blot. These studies will enable us to determine if a short duration or exposure to increased tissue levels of isoflavones will modulate biomarkers of cell differentiation (Cx43), adhesion (E-cadherin), proliferation (MIB-1), and cell growth and apoptosis (bcl-2. bax, p53, p21, Rb, EGF-R, cyclin D1, CDK5, CDK6) in benign, pre-malignant and malignant areas of breast epithelial tissues. Biomarker studies on the patients randomized on this study will be completed in early 2003. We have conducted a pilot study in six women, who took soy isoflavones 50 mg (Novasoy-Trademark) daily for three weeks. DNA was isolated from the nuclei of peripheral blood lymphocytes and analyzed for levels of 5-hydroxy-methyl-2'-deoxyuridine (5-OHmdU) by gas chromatography-mass spectrometry. The mean level of 5-OHmdU was decreased by 35% (relative to baseline) after 1 week and by about 50% after 2 weeks and 3 weeks of supplementation. Mean plasma levels of 8-isoprostane also decreased after supplementation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2001
- Accession Number
- ADA403703
Entities
People
- Omer Kucuk
Organizations
- Wayne State University