Induction of the phase 2 response in mouse and human skin by sulforaphane-containing broccoli sprout extracts

Albena T. Dinkova-Kostova, Jed W. Fahey, Kristina L. Wade, Stephanie N. Jenkins, Theresa A. Shapiro, Edward J. Fuchs, Michelle L. Kerns, Paul Talalay (Lead / Corresponding author)

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

The isothiocyanate sulforaphane was isolated from broccoli extracts in a bioactivity-guided fractionation as the principal and very potent inducer of cytoprotective phase 2 enzymes and subsequently shown to inhibit tumor development in animal models that involve various carcinogens and target organs. Because broccoli and broccoli sprouts are widely consumed, extracts obtained from them are viewed as convenient vehicles for sulforaphane delivery to humans. In relation to our current interest in devising strategies for protection against UV light-induced skin cancer, it was necessary to examine the safety and efficacy of topical application of sulforaphane-containing broccoli sprout extracts as single and multiple doses in both mice and humans. Topical application of an extract delivering 100 nmol sulforaphane/cm increased the protein levels of NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase A1, and heme oxygenase 1, three representative phase 2 enzymes, in mouse skin epidermis. Quantitative assessment of the activity of NQO1 24 h after dosing showed increases of 1.5- and 2.7-fold after application of single and multiple (thrice, every 24 h) doses, respectively. A dose-escalation safety study in healthy human subjects revealed no adverse reactions when doses as high as 340 nmol of sulforaphane in the form of broccoli sprout extracts were applied topically to the center of a 1-cm-diameter circle drawn on the volar forearm. A subsequent efficacy study showed that despite the interindividual differences in basal levels, the enzyme activity of NQO1 in homogenates of 3-mm full thickness skin punch biopsies increased in a dose-dependent manner, with maximum increases of 1.5- and 4.5-fold after application of 150 nmol doses, once or three times (at 24 h-intervals), respectively, thus providing direct evidence for induction of the phase 2 response in humans.

Original languageEnglish
Pages (from-to)847-851
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Volume16
Issue number4
DOIs
Publication statusPublished - 1 Apr 2007

Fingerprint

Brassica
Skin
Enzymes
Safety
Heme Oxygenase-1
Skin Neoplasms
Ultraviolet Rays
Glutathione Transferase
Forearm
Epidermis
Carcinogens
NAD
Healthy Volunteers
Oxidoreductases
Animal Models
sulforafan
Biopsy
Neoplasms
Proteins

Cite this

Dinkova-Kostova, Albena T. ; Fahey, Jed W. ; Wade, Kristina L. ; Jenkins, Stephanie N. ; Shapiro, Theresa A. ; Fuchs, Edward J. ; Kerns, Michelle L. ; Talalay, Paul. / Induction of the phase 2 response in mouse and human skin by sulforaphane-containing broccoli sprout extracts. In: Cancer Epidemiology Biomarkers and Prevention. 2007 ; Vol. 16, No. 4. pp. 847-851.
@article{684fbc2ee01a4ed89dc987400a398a64,
title = "Induction of the phase 2 response in mouse and human skin by sulforaphane-containing broccoli sprout extracts",
abstract = "The isothiocyanate sulforaphane was isolated from broccoli extracts in a bioactivity-guided fractionation as the principal and very potent inducer of cytoprotective phase 2 enzymes and subsequently shown to inhibit tumor development in animal models that involve various carcinogens and target organs. Because broccoli and broccoli sprouts are widely consumed, extracts obtained from them are viewed as convenient vehicles for sulforaphane delivery to humans. In relation to our current interest in devising strategies for protection against UV light-induced skin cancer, it was necessary to examine the safety and efficacy of topical application of sulforaphane-containing broccoli sprout extracts as single and multiple doses in both mice and humans. Topical application of an extract delivering 100 nmol sulforaphane/cm increased the protein levels of NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase A1, and heme oxygenase 1, three representative phase 2 enzymes, in mouse skin epidermis. Quantitative assessment of the activity of NQO1 24 h after dosing showed increases of 1.5- and 2.7-fold after application of single and multiple (thrice, every 24 h) doses, respectively. A dose-escalation safety study in healthy human subjects revealed no adverse reactions when doses as high as 340 nmol of sulforaphane in the form of broccoli sprout extracts were applied topically to the center of a 1-cm-diameter circle drawn on the volar forearm. A subsequent efficacy study showed that despite the interindividual differences in basal levels, the enzyme activity of NQO1 in homogenates of 3-mm full thickness skin punch biopsies increased in a dose-dependent manner, with maximum increases of 1.5- and 4.5-fold after application of 150 nmol doses, once or three times (at 24 h-intervals), respectively, thus providing direct evidence for induction of the phase 2 response in humans.",
author = "Dinkova-Kostova, {Albena T.} and Fahey, {Jed W.} and Wade, {Kristina L.} and Jenkins, {Stephanie N.} and Shapiro, {Theresa A.} and Fuchs, {Edward J.} and Kerns, {Michelle L.} and Paul Talalay",
year = "2007",
month = "4",
day = "1",
doi = "10.1158/1055-9965.EPI-06-0934",
language = "English",
volume = "16",
pages = "847--851",
journal = "Cancer Epidemiology, Biomarkers & Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research",
number = "4",

}

Induction of the phase 2 response in mouse and human skin by sulforaphane-containing broccoli sprout extracts. / Dinkova-Kostova, Albena T.; Fahey, Jed W.; Wade, Kristina L.; Jenkins, Stephanie N.; Shapiro, Theresa A.; Fuchs, Edward J.; Kerns, Michelle L.; Talalay, Paul (Lead / Corresponding author).

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 16, No. 4, 01.04.2007, p. 847-851.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Induction of the phase 2 response in mouse and human skin by sulforaphane-containing broccoli sprout extracts

AU - Dinkova-Kostova, Albena T.

AU - Fahey, Jed W.

AU - Wade, Kristina L.

AU - Jenkins, Stephanie N.

AU - Shapiro, Theresa A.

AU - Fuchs, Edward J.

AU - Kerns, Michelle L.

AU - Talalay, Paul

PY - 2007/4/1

Y1 - 2007/4/1

N2 - The isothiocyanate sulforaphane was isolated from broccoli extracts in a bioactivity-guided fractionation as the principal and very potent inducer of cytoprotective phase 2 enzymes and subsequently shown to inhibit tumor development in animal models that involve various carcinogens and target organs. Because broccoli and broccoli sprouts are widely consumed, extracts obtained from them are viewed as convenient vehicles for sulforaphane delivery to humans. In relation to our current interest in devising strategies for protection against UV light-induced skin cancer, it was necessary to examine the safety and efficacy of topical application of sulforaphane-containing broccoli sprout extracts as single and multiple doses in both mice and humans. Topical application of an extract delivering 100 nmol sulforaphane/cm increased the protein levels of NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase A1, and heme oxygenase 1, three representative phase 2 enzymes, in mouse skin epidermis. Quantitative assessment of the activity of NQO1 24 h after dosing showed increases of 1.5- and 2.7-fold after application of single and multiple (thrice, every 24 h) doses, respectively. A dose-escalation safety study in healthy human subjects revealed no adverse reactions when doses as high as 340 nmol of sulforaphane in the form of broccoli sprout extracts were applied topically to the center of a 1-cm-diameter circle drawn on the volar forearm. A subsequent efficacy study showed that despite the interindividual differences in basal levels, the enzyme activity of NQO1 in homogenates of 3-mm full thickness skin punch biopsies increased in a dose-dependent manner, with maximum increases of 1.5- and 4.5-fold after application of 150 nmol doses, once or three times (at 24 h-intervals), respectively, thus providing direct evidence for induction of the phase 2 response in humans.

AB - The isothiocyanate sulforaphane was isolated from broccoli extracts in a bioactivity-guided fractionation as the principal and very potent inducer of cytoprotective phase 2 enzymes and subsequently shown to inhibit tumor development in animal models that involve various carcinogens and target organs. Because broccoli and broccoli sprouts are widely consumed, extracts obtained from them are viewed as convenient vehicles for sulforaphane delivery to humans. In relation to our current interest in devising strategies for protection against UV light-induced skin cancer, it was necessary to examine the safety and efficacy of topical application of sulforaphane-containing broccoli sprout extracts as single and multiple doses in both mice and humans. Topical application of an extract delivering 100 nmol sulforaphane/cm increased the protein levels of NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase A1, and heme oxygenase 1, three representative phase 2 enzymes, in mouse skin epidermis. Quantitative assessment of the activity of NQO1 24 h after dosing showed increases of 1.5- and 2.7-fold after application of single and multiple (thrice, every 24 h) doses, respectively. A dose-escalation safety study in healthy human subjects revealed no adverse reactions when doses as high as 340 nmol of sulforaphane in the form of broccoli sprout extracts were applied topically to the center of a 1-cm-diameter circle drawn on the volar forearm. A subsequent efficacy study showed that despite the interindividual differences in basal levels, the enzyme activity of NQO1 in homogenates of 3-mm full thickness skin punch biopsies increased in a dose-dependent manner, with maximum increases of 1.5- and 4.5-fold after application of 150 nmol doses, once or three times (at 24 h-intervals), respectively, thus providing direct evidence for induction of the phase 2 response in humans.

UR - http://www.scopus.com/inward/record.url?scp=34247473917&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-06-0934

DO - 10.1158/1055-9965.EPI-06-0934

M3 - Article

C2 - 17416783

AN - SCOPUS:34247473917

VL - 16

SP - 847

EP - 851

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 4

ER -