MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kyle, E.
Right arrow Articles by Bergan, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kyle, E.
Right arrow Articles by Bergan, R.

0026-895X/97/020193-08$3.00/0
Copyright © by The American Society for Pharmacology and Experimental Therapeutics
All rights of reproduction in any form reserved.
MOLECULAR PHARMACOLOGY 51:193-200 (1997).

Genistein-Induced Apoptosis of Prostate Cancer Cells is Preceded by a Specific Decrease in Focal Adhesion Kinase Activity

Edward Kyle, Len Neckers, Chris Takimoto, Gregory Curt, and Raymond Bergan

Clinical Pharmacology Branch (E.K., L.N., R.B.), Navy Medical Oncology Branch (C.T.), and Clinical Director (G.C.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

Genistein (5,7,4'-trihydroxyisoflavone), an isoflavinoid found in soy beans, has been identified as potentially causal for the low incidence of metastatic prostate cancer (PCa) in certain countries. Although genistein-induced PCa cell adhesion has been identified as a possible causative mechanism, direct growth inhibition by genistein has been reported and also could be causal. If in vivo growth inhibition was significant, then growth inhibition should occur at concentrations attained with dietary consumption, the mechanism of growth inhibition should be relevant to PCa, and genistein (a broad-spectrum in vitro protein-tyrosine kinase inhibitor) should have relatively specific kinase inhibitory effects in vivo. These considerations were investigated by measuring growth inhibitory activity in a variety of PCa cell lines. Growth inhibitory effects were shown not to occur with concentrations below the low micromolar range (i.e., 3 logs above that attained in serum). In-depth mechanistic studies with the PC3-M metastatic variant cell line demonstrated that growth inhibition was independent of genistein's estrogenic effects. Genistein was shown to decrease the viability of nonadherent cells, suggesting a lack of dependence on cell adhesion for growth inhibition. However, important molecular and kinetic differences between genistein's effects on growth in adherent versus nonadherent cells were identified. Specific suppression of focal adhesion kinase activity (without global decreases in phosphotyrosine) was shown to precede induction of apoptosis, which was responsible for growth inhibition in adherent cells. These findings do not support an in vivo growth inhibitory role by genistein consumed in quantities associated with a soy-based diet. They do, however, identify genistein as a potential therapeutic agent for PCa and as a tool with which to study the control of apoptosis in PCa.

Copyright © by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Cancer Res.Home page
M. Lakshman, L. Xu, V. Ananthanarayanan, J. Cooper, C. H. Takimoto, I. Helenowski, J. C. Pelling, and R. C. Bergan
Dietary Genistein Inhibits Metastasis of Human Prostate Cancer in Mice
Cancer Res., March 15, 2008; 68(6): 2024 - 2032.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
L. Xu and R. C. Bergan
Genistein Inhibits Matrix Metalloproteinase Type 2 Activation and Prostate Cancer Cell Invasion by Blocking the Transforming Growth Factor beta-Mediated Activation of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2-27-kDa Heat Shock Protein Pathway
Mol. Pharmacol., September 1, 2006; 70(3): 869 - 877.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
T. K. Choueiri, T. Mekhail, T. E. Hutson, R. Ganapathi, G. E. Kelly, and R. M. Bukowski
Phase I trial of phenoxodiol delivered by continuous intravenous infusion in patients with solid cancer
Ann. Onc., May 1, 2006; 17(5): 860 - 865.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
M. Fukuda and R. Longnecker
Epstein-Barr Virus (EBV) Latent Membrane Protein 2A Regulates B-Cell Receptor-Induced Apoptosis and EBV Reactivation through Tyrosine Phosphorylation
J. Virol., July 1, 2005; 79(13): 8655 - 8660.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
X. Huang, S. Chen, L. Xu, Y. Liu, D. K. Deb, L. C. Platanias, and R. C. Bergan
Genistein Inhibits p38 Map Kinase Activation, Matrix Metalloproteinase Type 2, and Cell Invasion in Human Prostate Epithelial Cells
Cancer Res., April 15, 2005; 65(8): 3470 - 3478.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
G. G. Hillman, Y. Wang, O. Kucuk, M. Che, D. R. Doerge, M. Yudelev, M. C. Joiner, B. Marples, J. D. Forman, and F. H. Sarkar
Genistein potentiates inhibition of tumor growth by radiation in a prostate cancer orthotopic model
Mol. Cancer Ther., October 1, 2004; 3(10): 1271 - 1279.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. L. Bemis, J. L. Capodice, M. Desai, R. Buttyan, and A. E. Katz
A Concentrated Aglycone Isoflavone Preparation (GCP) That Demonstrates Potent Anti-Prostate Cancer Activity In vitro and In vivo
Clin. Cancer Res., August 1, 2004; 10(15): 5282 - 5292.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
J. A. Mobley, J. O. L'Esperance, M. Wu, C. J. Friel, R. H. Hanson, and S.-M. Ho
The novel estrogen 17{alpha}-20Z-21-[(4-amino)phenyl]-19-norpregna-1,3,5(10),20-tetraene-3,17{beta}-diol induces apoptosis in prostate cancer cell lines at nanomolar concentrations in vitro
Mol. Cancer Ther., May 1, 2004; 3(5): 587 - 596.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
C. H. Takimoto, K. Glover, X. Huang, S. A. Hayes, L. Gallot, M. Quinn, B. D. Jovanovic, A. Shapiro, L. Hernandez, A. Goetz, et al.
Phase I Pharmacokinetic and Pharmacodynamic Analysis of Unconjugated Soy Isoflavones Administered to Individuals with Cancer
Cancer Epidemiol. Biomarkers Prev., November 1, 2003; 12(11): 1213 - 1221.
[Abstract] [Full Text]

Home page
 J. Nutr.Home page
L. Yu, G. L. Blackburn, and J.-R. Zhou
Genistein and Daidzein Downregulate Prostate Androgen-Regulated Transcript-1 (PART-1) Gene Expression Induced by Dihydrotestosterone in Human Prostate LNCaP Cancer Cells
J. Nutr., February 1, 2003; 133(2): 389 - 392.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
M. Maggiolini, A. Vivacqua, A. Carpino, D. Bonofiglio, G. Fasanella, M. Salerno, D. Picard, and S. Ando
The Mutant Androgen Receptor T877A Mediates the Proliferative but Not the Cytotoxic Dose-Dependent Effects of Genistein and Quercetin on Human LNCaP Prostate Cancer Cells
Mol. Pharmacol., November 1, 2002; 62(5): 1027 - 1035.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Mentor-Marcel, C. A. Lamartiniere, I.-E. Eltoum, N. M. Greenberg, and A. Elgavish
Genistein in the Diet Reduces the Incidence of Poorly Differentiated Prostatic Adenocarcinoma in Transgenic Mice (TRAMP)
Cancer Res., September 1, 2001; 61(18): 6777 - 6782.
[Abstract] [Full Text] [PDF]

Home page
 CA Cancer J ClinHome page
J. Brown, T. Byers, K. Thompson, B. Eldridge, C. Doyle, A. M. Williams, and American Cancer Society Workgroup on Nutrition and
Nutrition During and After Cancer Treatment: A Guide for Informed Choices by Cancer Survivors
CA Cancer J Clin, May 1, 2001; 51(3): 153 - 181.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. G. Hillman, J. D. Forman, O. Kucuk, M. Yudelev, R. L. Maughan, J. Rubio, A. Layer, S. Tekyi-Mensah, J. Abrams, and F. H. Sarkar
Genistein Potentiates the Radiation Effect on Prostate Carcinoma Cells
Clin. Cancer Res., February 1, 2001; 7(2): 382 - 390.
[Abstract] [Full Text]

Home page
 J. Nutr.Home page
L. K. Leung and T. T. Wang
Bcl-2 Is Not Reduced in the Death of MCF-7 Cells at Low Genistein Concentration
J. Nutr., December 1, 2000; 130(12): 2922 - 2926.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
M. J Messina
Legumes and soybeans: overview of their nutritional profiles and health effects
Am. J. Clinical Nutrition, September 1, 1999; 70(3): 439S - 450.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. C. Bergan, E. Reed, C. E. Myers, D. Headlee, O. Brawley, H.-K. Cho, W. D. Figg, A. Tompkins, W. M. Linehan, D. Kohler, et al.
A Phase II Study of High-Dose Tamoxifen in Patients with Hormone-refractory Prostate Cancer
Clin. Cancer Res., September 1, 1999; 5(9): 2366 - 2373.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
W. Zheng, Q. Dai, L. J. Custer, X.-O. Shu, W.-Q. Wen, F. Jin, and A. A. Franke
Urinary Excretion of Isoflavonoids and the Risk of Breast Cancer
Cancer Epidemiol. Biomarkers Prev., January 1, 1999; 8(1): 35 - 40.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1997 by the American Society for Pharmacology and Experimental Therapeutics