![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
,2,3
Departments of * Pharmacology and Therapeutics, Surgery, Molecular Genetics and Microbiology, College of Medicine, Analytical Toxicology Core Laboratory, College of Veterinary Medicine, and ** Department of Statistics, College of Liberal Arts and Sciences, University of Florida, Gainesville, FL 32610
3 To whom correspondence should be addressed. E-mail: lrice{at}ufl.edu
ABSTRACT
High consumption of soy isoflavones in Asian diets has been correlated with a lower incidence of clinically important cases of prostate cancer. The chemopreventive properties of these diets may result from an interaction of several types of isoflavones, including genistein and daidzein. The present study investigated the effects of a soy isoflavone concentrate (ISF) on growth and gene expression profiles of PC-3 human prostate cancer cells. Trypan blue exclusion and [3H]-thymidine incorporation assays showed that ISF decreased cell viability and caused a dose-dependent inhibition of DNA synthesis, respectively, with 50% inhibition (IC50) of DNA synthesis at 52 mg/L (P = 0.05). The glucoside conjugates of genistein and daidzein in ISF were converted to bioactive free aglycones in cell culture in association with the inhibition of DNA synthesis. Flow cytometry and Western immunoblot analyses showed that ISF at 200 mg/L caused an accumulation of cells in the G2/M phase of the cell cycle (P < 0.05) and decreased cyclin A by 20% (P < 0.05), respectively. The effect of ISF on the gene expression profile of PC-3 cells was analyzed using Affymetrix oligonucleotide DNA microarrays that interrogate 
17,000 human genes. Of the 75 genes altered by ISF, 28 were upregulated and 47 were downregulated (P < 0.05). Further analysis showed that IL-8, matrix metalloproteinase 13, inhibin ß A, follistatin, and fibronectin mRNA levels were significantly reduced, whereas the expression of p21CIP1, a major cell cycle inhibitory protein, was increased. The effects of ISF on the expression of IL-8 and p21CIP1 mRNA and protein were validated at high and low ISF concentrations. Our data show that ISF inhibits the growth of PC-3 cells through modulation of cell cycle progression and the expression of genes involved in cell cycle regulation, metastasis, and angiogenesis.
KEY WORDS: • interleukin-8 • isoflavones • microarray • p21CIP1 • prostate
This article has been cited by other articles:
|
|
 |
|
  R. Xiao, L. J Hennings, T. M Badger, and F. A Simmen Fetal programing of colon cancer in adult rats: correlations with altered neonatal growth trajectory, circulating IGF-I and IGF binding proteins, and testosterone J. Endocrinol., October 1, 2007; 195(1): 79 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Theodoratou, J. Kyle, R. Cetnarskyj, S. M. Farrington, A. Tenesa, R. Barnetson, M. Porteous, M. Dunlop, and H. Campbell Dietary Flavonoids and the Risk of Colorectal Cancer Cancer Epidemiol. Biomarkers Prev., April 1, 2007; 16(4): 684 - 693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Rice, R. Handayani, Y. Cui, T. Medrano, V. Samedi, H. Baker, N. J. Szabo, C. J. Rosser, S. Goodison, and K. T. Shiverick Soy Isoflavones Exert Differential Effects on Androgen Responsive Genes in LNCaP Human Prostate Cancer Cells J. Nutr., April 1, 2007; 137(4): 964 - 972. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Walczak and M. A. Carducci Prostate Cancer: A Practical Approach to Current Management of Recurrent Disease Mayo Clin. Proc., February 1, 2007; 82(2): 243 - 249. [Abstract] [Full Text] [PDF]
|
|
