.JPG?ad=18503&adview=true)
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Surgery, Molecular Biology Laboratory, Cancer Hospital/Cancer Institute, Shanghai Medical University, Shanghai, 200032. People's Republic of China [Z-M. S., J. W., Z-Z. S.] and Department of Pathology and Revlon/UCLA Breast Center, UCLA School of Medicine, Los Angeles, California 90024 [Z-M. S., S. H. B.]
Dietary genistein, a natural flavone compound found in soy, has been proposed to be responsible for the low rate of breast cancer in Asian women. The cellular mechanisms of genistein's chemopreventive effects in vivo have been largely unexplored. In our previous studies, we found that genistein exerted pronounced antiproliferative effects on both estrogen receptor-positive and -negative human breast carcinoma cells through G2-M arrest, induction of p21WAF1/CIP1 expression, and apoptosis. Because chemopreventive effects need not be limited to antiproliferation, we decided to examine whether genistein exerted other suppressive effects on breast carcinoma progression. Genistein inhibited invasion in vitro of MCF-7 and MDA-MB-231 cells. This inhibition was characterized by down-regulation of MMP (matrix metalloproteinase)-9 and up-regulation of tissue inhibitor of metalloproteinase-1, the former of which was transcriptionally regulated at activation protein-1 sites in the MMP-9 promoter. Genistein's in vitro effects on MMP-9 and tissue inhibitor of metalloproteinase-1 were also demonstrated in in vivo studies in nude mouse xenografts of MDA-MB-231 and MCF-7 cells. In these xenograft studies, genistein inhibited tumor growth, stimulated apoptosis, and up-regulated p21WAF1/CIP1 expression. In the MDA-MB-231 xenograft, genistein also inhibited angiogenesis by decreasing vessel density and decreasing the levels of vascular endothelial growth factor and transforming growth factor-ß1. These in vitro and in vivo studies demonstrate that genistein exerts multiple suppressive effects on breast carcinoma cells, suggesting that its mechanism of chemoprevention is pleiotropic.
1 Supported by the National Natural Science Foundation of China 39670803 and USPHS Grants CA71195, CA40225, and CA01351.
2 To whom requests for reprints should be addressed, at Department of Pathology, UCLA School of Medicine, Los Angeles, CA 90024. Fax: (310) 441-1248; E-mail: sbarsky@ucla.edu.
Received 6/ 3/98. Accepted 9/ 2/98.
This article has been cited by other articles:
|
|
 |
|
  S. Rice and S. A Whitehead Phytoestrogens and breast cancer -promoters or protectors? Endocr. Relat. Cancer, December 1, 2006; 13(4): 995 - 1015. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-O. Yoon, S. Shin, H.-J. Lee, H.-K. Chun, and A.-S. Chung Isoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt-dependent matrix metalloproteinase-9 expression. Mol. Cancer Ther., November 1, 2006; 5(11): 2666 - 2675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Messina, W. McCaskill-Stevens, and J. W. Lampe Addressing the soy and breast cancer relationship: review, commentary, and workshop proceedings. J Natl Cancer Inst, September 20, 2006; 98(18): 1275 - 1284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Gallo, C. Ferlini, M. Fabrizi, S. Prislei, and G. Scambia Lack of stimulatory activity of a Phytoestrogen-containing soy extract on the growth of breast cancer tumors in mice Carcinogenesis, July 1, 2006; 27(7): 1404 - 1409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Trock, L. Hilakivi-Clarke, and R. Clarke Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst, April 5, 2006; 98(7): 459 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Z. Fang, D. Chen, Y. Sun, Z. Jin, J. K. Christman, and C. S. Yang Reversal of Hypermethylation and Reactivation of p16INK4a, RAR{beta}, and MGMT Genes by Genistein and Other Isoflavones from Soy Clin. Cancer Res., October 1, 2005; 11(19): 7033 - 7041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-W. Chen, S.-C. Huang, S.-Y. Lin-Shiau, and J.-K. Lin Bowman-Birk inhibitor abates proteasome function and suppresses the proliferation of MCF7 breast cancer cells through accumulation of MAP kinase phosphatase-1 Carcinogenesis, July 1, 2005; 26(7): 1296 - 1306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Wood, T. C. Register, M. S. Anthony, N. D. Kock, and J. M. Cline Breast and Uterine Effects of Soy Isoflavones and Conjugated Equine Estrogens in Postmenopausal Female Monkeys J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3462 - 3468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Miyata, T. Sato, M. Yano, and A. Ito Activation of protein kinase C {beta}II/{varepsilon}-c-Jun NH2-terminal kinase pathway and inhibition of mitogen-activated protein/extracellular signal-regulated kinase 1/2 phosphorylation in antitumor invasive activity induced by the polymethoxy flavonoid, nobiletin Mol. Cancer Ther., July 1, 2004; 3(7): 839 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-F. Chen and M.-S. Wong Genistein Enhances Insulin-Like Growth Factor Signaling Pathway in Human Breast Cancer (MCF-7) Cells J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2351 - 2359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.T.T. Nguyen, E. Tran, T.H. Nguyen, P.T. Do, T.H. Huynh, and H. Huynh The role of activated MEK-ERK pathway in quercetin-induced growth inhibition and apoptosis in A549 lung cancer cells Carcinogenesis, May 1, 2004; 25(5): 647 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Sartippour, Z.-M. Shao, D. Heber, P. Beatty, L. Zhang, C. Liu, L. Ellis, W. Liu, V. L. Go, and M. N. Brooks Green Tea Inhibits Vascular Endothelial Growth Factor (VEGF) Induction in Human Breast Cancer Cells J. Nutr., August 1, 2002; 132(8): 2307 - 2311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. I. Block, A. Constantinou, L. Hilakivi-Clarke, C. Hughes, D. Tripathy, J. A. Tice, K. Block, and K. Block Point-Counterpoint: Soy Intake for Breast Cancer Patients Integr Cancer Ther, March 1, 2002; 1(1): 90 - 100. [PDF]
|
|
|
|
|
|
M. Messina, C. Gardner, and S. Barnes Gaining Insight into the Health Effects of Soy but a Long Way Still to Go: Commentary on the Fourth International Symposium on the Role of Soy in Preventing and Treating Chronic Disease J. Nutr., March 1, 2002; 132(3): 547S - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sato, L. Koike, Y. Miyata, M. Hirata, Y. Mimaki, Y. Sashida, M. Yano, and A. Ito Inhibition of Activator Protein-1 Binding Activity and Phosphatidylinositol 3-Kinase Pathway by Nobiletin, a Polymethoxy Flavonoid, Results in Augmentation of Tissue Inhibitor of Metalloproteinases-1 Production and Suppression of Production of Matrix Metalloproteinases-1 and -9 in Human Fibrosarcoma HT-1080 Cells Cancer Res., February 1, 2002; 62(4): 1025 - 1029. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. TOSETTI, N. FERRARI, S. DE FLORA, and A. ALBINI Angioprevention': angiogenesis is a common and key target for cancer chemopreventive agents FASEB J, January 1, 2002; 16(1): 2 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Alhasan, O. Aranha, and F. H. Sarkar Genistein Elicits Pleiotropic Molecular Effects on Head and Neck Cancer Cells Clin. Cancer Res., December 1, 2001; 7(12): 4174 - 4181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Messina and C. L. Loprinzi Soy for Breast Cancer Survivors: A Critical Review of the Literature J. Nutr., November 1, 2001; 131(11): 3095S - 3108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Kamath, A. Meydani, F. Foss, and A. Kuliopulos Signaling from Protease-activated Receptor-1 Inhibits Migration and Invasion of Breast Cancer Cells Cancer Res., August 1, 2001; 61(15): 5933 - 5940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Upadhyay, M. Neburi, S. R. Chinni, S. Alhasan, F. Miller, and F. H. Sarkar Differential Sensitivity of Normal and Malignant Breast Epithelial Cells to Genistein Is Partly Mediated by p21WAF1 Clin. Cancer Res., June 1, 2001; 7(6): 1782 - 1789. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-M. Lin, B.-K. Moon, F. Yu, and H.-R. C. Kim Galectin-3 mediates genistein-induced G2/M arrest and inhibits apoptosis Carcinogenesis, November 1, 2000; 21(11): 1941 - 1945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tamir, M. Eizenberg, D. Somjen, N. Stern, R. Shelach, A. Kaye, and J. Vaya Estrogenic and Antiproliferative Properties of Glabridin from Licorice in Human Breast Cancer Cells Cancer Res., October 1, 2000; 60(20): 5704 - 5709. [Abstract] [Full Text]
|
|
|
|
|
|
R. C. Santell, N. Kieu, and W. G. Helferich Genistein Inhibits Growth of Estrogen-Independent Human Breast Cancer Cells in Culture but Not in Athymic Mice J. Nutr., July 1, 2000; 130(7): 1665 - 1669. [Abstract] [Full Text]
|
|
|
|
 |
|
 J.-M. Darbon, M. Penary, N. Escalas, F. Casagrande, F. Goubin-Gramatica, C. Baudouin, and B. Ducommun Distinct Chk2 Activation Pathways Are Triggered by Genistein and DNA-damaging Agents in Human Melanoma Cells J. Biol. Chem., May 12, 2000; 275(20): 15363 - 15369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Messina Soy, soy phytoestrogens (isoflavones), and breast cancer Am. J. Clinical Nutrition, October 1, 1999; 70(4): 574 - 575. [Full Text]
|
|
|
|
|
|
S.-O. Yoon, M.-M. Kim, and A.-S. Chung Inhibitory Effect of Selenite on Invasion of HT1080 Tumor Cells J. Biol. Chem., June 1, 2001; 276(23): 20085 - 20092. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
