Carcinogenesis Advance Access originally published online on March 7, 2007
Carcinogenesis 2007 28(7):1485-1490; doi:10.1093/carcin/bgm049
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast
1 Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
2 Department of Pharmacology and Molecular Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
3 Department of Surgery, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
4 Department of Pathology, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
5 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
6 Department of Oncology, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
7 Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
* To whom correspondence should be addressed. Tel: +1 410 614 1112; Fax: +1 410 614 2632; Email: kvisvana{at}jhsph.edu
Consumers of higher levels of Brassica vegetables, particularly those of the genus Brassica (broccoli, Brussels sprouts and cabbage), reduce their susceptibility to cancer at a variety of organ sites. Brassica vegetables contain high concentrations of glucosinolates that can be hydrolyzed by the plant enzyme, myrosinase, or intestinal microflora to isothiocyanates, potent inducers of cytoprotective enzymes and inhibitors of carcinogenesis. Oral administration of either the isothiocyanate, sulforaphane, or its glucosinolate precursor, glucoraphanin, inhibits mammary carcinogenesis in rats treated with 7,12-dimethylbenz[a]anthracene. In this study, we sought to determine whether sulforaphane exerts a direct chemopreventive action on animal and human mammary tissue. The pharmacokinetics and pharmacodynamics of a single 150 µmol oral dose of sulforaphane were evaluated in the rat mammary gland. We detected sulforaphane metabolites at concentrations known to alter gene expression in cell culture. Elevated cytoprotective NAD(P)H:quinone oxidoreductase (NQO1) and heme oxygenase-1 (HO-1) gene transcripts were measured using quantitative real-time polymerase chain reaction. An observed 3-fold increase in NQO1 enzymatic activity, as well as 4-fold elevated immunostaining of HO-1 in rat mammary epithelium, provides strong evidence of a pronounced pharmacodynamic action of sulforaphane. In a subsequent pilot study, eight healthy women undergoing reduction mammoplasty were given a single dose of a broccoli sprout preparation containing 200 µmol of sulforaphane. Following oral dosing, sulforaphane metabolites were readily measurable in human breast tissue enriched for epithelial cells. These findings provide a strong rationale for evaluating the protective effects of a broccoli sprout preparation in clinical trials of women at risk for breast cancer.
Abbreviations: BPP, Brassica Protection Products LLC; DTC, dithiocarbamate; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HO-1, heme oxygenase-1; NRF2, nuclear factor erythroid 2-related factor 2; NQO1, NAD(P)H:quinone oxidoreductase; PCR, polymerase chain reaction
Received November 30, 2006; revised February 4, 2007; accepted February 22, 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C.-W. Lin, S.-C. Shen, W.-C. Hou, L.-Y. Yang, and Y.-C. Chen Heme oxygenase-1 inhibits breast cancer invasion via suppressing the expression of matrix metalloproteinase-9 Mol. Cancer Ther., May 1, 2008; 7(5): 1195 - 1206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Yu, B. M. Dietz, T. Dunlap, I. Kastrati, D. D. Lantvit, C. R. Overk, P. Yao, Z. Qin, J. L. Bolton, and G. R.J. Thatcher Structural modulation of reactivity/activity in design of improved benzothiophene selective estrogen receptor modulators: induction of chemopreventive mechanisms Mol. Cancer Ther., September 1, 2007; 6(9): 2418 - 2428. [Abstract] [Full Text] [PDF]
|
|