| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Urology, Stanford University Medical Center, Stanford, California 94305-5118
Two population-based, case-control studies have documented reduced risk of prostate cancer in men who consume cruciferous vegetables. Cruciferae contain high levels of the isothiocyanate sulforaphane. Sulforaphane is known to bolster the defenses of cells against carcinogens through up-regulation of enzymes of carcinogen defense (phase 2 enzymes). Prostate cancer is characterized by an early and near universal loss of expression of the phase 2 enzyme glutathione S-transferase (GST)-
. We tested whether sulforaphane may act in prostatic cells by increasing phase 2 enzyme expression. The human prostate cancer cell lines LNCaP, MDA PCa 2a, MDA PCa 2b, PC-3, and TSU-Pr1 were treated with 0.1–15 µM sulforaphane in vitro. LNCaP was also treated with an aqueous extract of broccoli sprouts. Quinone reductase enzymatic activity, a surrogate of global phase 2 enzyme activity, was assayed by the menadione-coupled reduction of tetrazolium dye. Expression of NQO-1, GST-
, 
-glutamylcysteine synthetase-heavy and -light chains, and microsomal GST was assessed by Northern blot analysis. Sulforaphane and broccoli sprout extract potently induce quinone reductase activity in cultured prostate cells, and this induction appears to be mediated by increased transcription of the NQO-1 gene. Sulforaphane also induces expression of -glutamylcysteine synthetase light subunit but not the heavy subunit, and this induction is associated with moderate increases in intracellular glutathione levels. Microsomal and -class glutathione transferases were also induced transcriptionally. Sulforaphane induces phase 2 enzyme expression and activity significantly in human prostatic cells. This induction is accompanied by, but not because of, increased intracellular glutathione synthesis. Our findings may help explain the observed inverse correlation between consumption of cruciferae and prostate cancer risk.
This article has been cited by other articles:
|
|
 |
|
  V. A. Kirsh, U. Peters, S. T. Mayne, A. F. Subar, N. Chatterjee, C. C. Johnson, and R. B. Hayes Prospective Study of Fruit and Vegetable Intake and Risk of Prostate Cancer J Natl Cancer Inst, August 1, 2007; 99(15): 1200 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Pappa, J. Strathmann, M. Lowinger, H. Bartsch, and C. Gerhauser Quantitative combination effects between sulforaphane and 3,3'-diindolylmethane on proliferation of human colon cancer cells in vitro Carcinogenesis, July 1, 2007; 28(7): 1471 - 1477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Gasper, M. Traka, J. R. Bacon, J. A. Smith, M. A. Taylor, C. J. Hawkey, D. A. Barrett, and R. F. Mithen Consuming Broccoli Does Not Induce Genes Associated with Xenobiotic Metabolism and Cell Cycle Control in Human Gastric Mucosa J. Nutr., July 1, 2007; 137(7): 1718 - 1724. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Herman-Antosiewicz, H. Xiao, K. L. Lew, and S. V. Singh Induction of p21 protein protects against sulforaphane-induced mitotic arrest in LNCaP human prostate cancer cell line Mol. Cancer Ther., May 1, 2007; 6(5): 1673 - 1681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Chang, J. Bigler, Y. Schwarz, S. S. Li, L. Li, I. B. King, J. D. Potter, and J. W. Lampe UGT1A1 Polymorphism Is Associated with Serum Bilirubin Concentrations in a Randomized, Controlled, Fruit and Vegetable Feeding Trial J. Nutr., April 1, 2007; 137(4): 890 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Choi, K. L. Lew, H. Xiao, A. Herman-Antosiewicz, D. Xiao, C. K. Brown, and S. V. Singh D,L-Sulforaphane-induced cell death in human prostate cancer cells is regulated by inhibitor of apoptosis family proteins and Apaf-1 Carcinogenesis, January 1, 2007; 28(1): 151 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Ritz, J. Wan, and D. Diaz-Sanchez Sulforaphane-stimulated phase II enzyme induction inhibits cytokine production by airway epithelial cells stimulated with diesel extract Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L33 - L39. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Fowke, J. D. Morrow, S. Motley, R. M. Bostick, and R. M. Ness Brassica vegetable consumption reduces urinary F2-isoprostane levels independent of micronutrient intake Carcinogenesis, October 1, 2006; 27(10): 2096 - 2102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Saxe, J. M. Major, J. Y. Nguyen, K. M. Freeman, T. M. Downs, and C. E. Salem Potential attenuation of disease progression in recurrent prostate cancer with plant-based diet and stress reduction. Integr Cancer Ther, September 1, 2006; 5(3): 206 - 213. [Abstract] [PDF]
|
|
|
|
|
|
J. Y. Nguyen, J. M. Major, C. J. Knott, K. M. Freeman, T. M. Downs, and G. A. Saxe Adoption of a plant-based diet by patients with recurrent prostate cancer. Integr Cancer Ther, September 1, 2006; 5(3): 214 - 223. [Abstract] [PDF]
|
|
|
|
|
|
C. Xu, X. Yuan, Z. Pan, G. Shen, J.-H. Kim, S. Yu, T. O. Khor, W. Li, J. Ma, and A.-N. T. Kong Mechanism of action of isothiocyanates: the induction of ARE-regulated genes is associated with activation of ERK and JNK and the phosphorylation and nuclear translocation of Nrf2. Mol. Cancer Ther., August 1, 2006; 5(8): 1918 - 1926. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Herman-Antosiewicz, D. E. Johnson, and S. V. Singh Sulforaphane Causes Autophagy to Inhibit Release of Cytochrome c and Apoptosis in Human Prostate Cancer Cells Cancer Res., June 1, 2006; 66(11): 5828 - 5835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Xu, G. Shen, X. Yuan, J.-h. Kim, A. Gopalkrishnan, Y.-S. Keum, S. Nair, and A.-N. T. Kong ERK and JNK signaling pathways are involved in the regulation of activator protein 1 and cell death elicited by three isothiocyanates in human prostate cancer PC-3 cells Carcinogenesis, March 1, 2006; 27(3): 437 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kim, E. H. Kim, Y. W. Eom, W.-H. Kim, T. K. Kwon, S. J. Lee, and K. S. Choi Sulforaphane Sensitizes Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Resistant Hepatoma Cells to TRAIL-Induced Apoptosis through Reactive Oxygen Species-Mediated Up-regulation of DR5 Cancer Res., February 1, 2006; 66(3): 1740 - 1750. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V Gasper, A. Al-janobi, J. A Smith, J. R Bacon, P. Fortun, C. Atherton, M. A Taylor, C. J Hawkey, D. A Barrett, and R. F Mithen Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli Am. J. Clinical Nutrition, December 1, 2005; 82(6): 1283 - 1291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Traka, A. V. Gasper, J. A. Smith, C. J. Hawkey, Y. Bao, and R. F. Mithen Transcriptome Analysis of Human Colon Caco-2 Cells Exposed to Sulforaphane J. Nutr., August 1, 2005; 135(8): 1865 - 1872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. Singh, S. K. Srivastava, S. Choi, K. L. Lew, J. Antosiewicz, D. Xiao, Y. Zeng, S. C. Watkins, C. S. Johnson, D. L. Trump, et al. Sulforaphane-induced Cell Death in Human Prostate Cancer Cells Is Initiated by Reactive Oxygen Species J. Biol. Chem., May 20, 2005; 280(20): 19911 - 19924. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Jones, S. E. DePrimo, M. L. Whitfield, and J. D. Brooks Resveratrol-Induced Gene Expression Profiles in Human Prostate Cancer Cells Cancer Epidemiol. Biomarkers Prev., March 1, 2005; 14(3): 596 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. McWalter, L. G. Higgins, L. I. McLellan, C. J. Henderson, L. Song, P. J. Thornalley, K. Itoh, M. Yamamoto, and J. D. Hayes Transcription Factor Nrf2 Is Essential for Induction of NAD(P)H:Quinone Oxidoreductase 1, Glutathione S-Transferases, and Glutamate Cysteine Ligase by Broccoli Seeds and Isothiocyanates J. Nutr., December 1, 2004; 134(12): 3499S - 3506S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N.-A. Pham, J. W. Jacobberger, A. D. Schimmer, P. Cao, M. Gronda, and D. W. Hedley The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor growth in severe combined immunodeficient mice Mol. Cancer Ther., October 1, 2004; 3(10): 1239 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. T. Jackson and K. W. Singletary Sulforaphane Inhibits Human MCF-7 Mammary Cancer Cell Mitotic Progression and Tubulin Polymerization J. Nutr., September 1, 2004; 134(9): 2229 - 2236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Chiao, H. Wu, G. Ramaswamy, C. C. Conaway, F.-L. Chung, L. Wang, and D. Liu Ingestion of an isothiocyanate metabolite from cruciferous vegetables inhibits growth of human prostate cancer cell xenografts by apoptosis and cell cycle arrest Carcinogenesis, August 1, 2004; 25(8): 1403 - 1408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang and G. B. Gordon A strategy for cancer prevention: Stimulation of the Nrf2-ARE signaling pathway Mol. Cancer Ther., July 1, 2004; 3(7): 885 - 893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. Singh, A. Herman-Antosiewicz, A. V. Singh, K. L. Lew, S. K. Srivastava, R. Kamath, K. D. Brown, L. Zhang, and R. Baskaran Sulforaphane-induced G2/M Phase Cell Cycle Arrest Involves Checkpoint Kinase 2-mediated Phosphorylation of Cell Division Cycle 25C J. Biol. Chem., June 11, 2004; 279(24): 25813 - 25822. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhao, M. L. Whitfield, T. Xu, D. Botstein, and J. D. Brooks Diverse Effects of Methylseleninic Acid on the Transcriptional Program of Human Prostate Cancer Cells Mol. Biol. Cell, February 1, 2004; 15(2): 506 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Singh, D. Xiao, K. L. Lew, R. Dhir, and S. V. Singh Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo Carcinogenesis, January 1, 2004; 25(1): 83 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Giovannucci, E. B. Rimm, Y. Liu, M. J. Stampfer, and W. C. Willett A Prospective Study of Cruciferous Vegetables and Prostate Cancer Cancer Epidemiol. Biomarkers Prev., December 1, 2003; 12(12): 1403 - 1409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-R. Kim, R. Hu, Y.-S. Keum, V. Hebbar, G. Shen, S. S. Nair, and A-N. T. Kong Effects of Glutathione on Antioxidant Response Element-Mediated Gene Expression and Apoptosis Elicited by Sulforaphane Cancer Res., November 1, 2003; 63(21): 7520 - 7525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Saxe Integrative Tumor Board: Recently Diagnosed Prostate Cancer Integr Cancer Ther, March 1, 2003; 2(1): 65 - 73. [PDF]
|
|
|
|
|
|
J. D. Brooks, M. F. Goldberg, L. A. Nelson, D. Wu, and W. G. Nelson Identification of Potential Prostate Cancer Preventive Agents through Induction of Quinone Reductase in Vitro Cancer Epidemiol. Biomarkers Prev., September 1, 2002; 11(9): 868 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. BRADLOW and D. W. SEPKOVIC Diet and Breast Cancer Ann. N.Y. Acad. Sci., June 1, 2002; 963(1): 247 - 267. [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 | Cell Growth & Differentiation |
