TY - JOUR
T1 - Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast
AU - Cornblatt, Brian S.
AU - Ye, Lingxiang
AU - Dinkova-Kostova, Albena T.
AU - Erb, Melanie
AU - Fahey, Jed W.
AU - Singh, Navin K.
AU - Chen, Min Shue A.
AU - Stierer, Tracey
AU - Garrett-Mayer, Elizabeth
AU - Argani, Pedram
AU - Davidson, Nancy E.
AU - Talalay, Paul
AU - Kensler, Thomas W.
AU - Visvanathan, Kala
N1 - Funding Information:
This research was supported by National Institutes of Health grants, Breast Spore P50 CA088843, Breast Cancer Research Foundation and the Lewis B. and Dorothy Cullman Foundation. K.V. is a recipient of an ASCO Career Development Award and a KO7 Preventive Oncology Academic Award CA11948 from the National Cancer Institute. B.S.C. was supported by T32 ES07141. We thank Patrick Dolan for assistance with animal care and Brian Schofield, Jessica Hicks, Kristen Lecksell and Angelo DeMarzo for their assistance with immunohistochemical assays. We thank Katherine Stephenson and Kristina L.Wade for assistance in making the broccoli preparation and Deborah Santor, Anita Mayfield and Amy Gross for assistance with the clinical studies.
PY - 2007/7
Y1 - 2007/7
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/bgm049
DO - 10.1093/carcin/bgm049
M3 - Article
C2 - 17347138
AN - SCOPUS:34547795788
SN - 0143-3334
VL - 28
SP - 1485
EP - 1490
JO - Carcinogenesis
JF - Carcinogenesis
IS - 7
ER -