Suppression of Estrogen Biosynthesis by Procyanidin Dimers in Red Wine and Grape Seeds

Elizabeth T. Eng, JingJing Ye, Dudley Williams, Sheryl Phung, Roger E. Moore, Mary K. Young, Ugis Gruntmanis, Glenn Braunstein, Shiuan Chen

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

In breast cancer, in situ estrogen production has been demonstrated to play a major role in promoting tumor growth. Aromatase is the enzyme responsible for the conversion of androgen substrates into estrogens. This enzyme is highly expressed in breast cancer tissue compared with normal breast tissue. A wine extract fraction was recently isolated from red wine that exhibited a potent inhibitory action on aromatase activity. Using UV absorbance analysis, high-performance liquid chromatography profiling, accurate mass-mass spectrometry, and nanospray tandem mass spectrometry, most of the compounds in our red wine fraction were identified as procyanidin B dimers that were shown to be aromatase inhibitors. These chemicals have been found in high levels in grape seeds. Inhibition kinetic analysis on the most potent procyanidin B dimer has revealed that it competes with the binding of the androgen substrate with a Ki value of 6 μM. Because mutations at Asp-309, Ser-378, and His-480 of aromatase significantly affected the binding of the procyanidin B dimer, these active site residues are thought to be important residues that interact with this phytochemical. The in vivo efficacy of procyanidin B dimers was evaluated in an aromatase-transfected MCF-7 breast cancer xenograft model. The procyanidin B dimers were able to reduce androgen-dependent tumor growth, indicating that these chemicals suppress in situ estrogen formation. These in vitro and in vivo studies demonstrated that procyanidin B dimers in red wine and grape seeds could be used as chemopreventive agents against breast cancer by suppressing in situ estrogen biosynthesis.

Original languageEnglish (US)
Pages (from-to)8516-8522
Number of pages7
JournalCancer Research
Volume63
Issue number23
StatePublished - Dec 1 2003

Fingerprint

Vitis
Wine
Seeds
Estrogens
Aromatase
Breast Neoplasms
Androgens
Aromatase Inhibitors
Phytochemicals
Enzymes
Growth
Tandem Mass Spectrometry
Heterografts
procyanidin
procyanidin B
Mass Spectrometry
Catalytic Domain
Neoplasms
Breast
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Eng, E. T., Ye, J., Williams, D., Phung, S., Moore, R. E., Young, M. K., ... Chen, S. (2003). Suppression of Estrogen Biosynthesis by Procyanidin Dimers in Red Wine and Grape Seeds. Cancer Research, 63(23), 8516-8522.

Suppression of Estrogen Biosynthesis by Procyanidin Dimers in Red Wine and Grape Seeds. / Eng, Elizabeth T.; Ye, JingJing; Williams, Dudley; Phung, Sheryl; Moore, Roger E.; Young, Mary K.; Gruntmanis, Ugis; Braunstein, Glenn; Chen, Shiuan.

In: Cancer Research, Vol. 63, No. 23, 01.12.2003, p. 8516-8522.

Research output: Contribution to journalArticle

Eng, ET, Ye, J, Williams, D, Phung, S, Moore, RE, Young, MK, Gruntmanis, U, Braunstein, G & Chen, S 2003, 'Suppression of Estrogen Biosynthesis by Procyanidin Dimers in Red Wine and Grape Seeds', Cancer Research, vol. 63, no. 23, pp. 8516-8522.
Eng ET, Ye J, Williams D, Phung S, Moore RE, Young MK et al. Suppression of Estrogen Biosynthesis by Procyanidin Dimers in Red Wine and Grape Seeds. Cancer Research. 2003 Dec 1;63(23):8516-8522.
Eng, Elizabeth T. ; Ye, JingJing ; Williams, Dudley ; Phung, Sheryl ; Moore, Roger E. ; Young, Mary K. ; Gruntmanis, Ugis ; Braunstein, Glenn ; Chen, Shiuan. / Suppression of Estrogen Biosynthesis by Procyanidin Dimers in Red Wine and Grape Seeds. In: Cancer Research. 2003 ; Vol. 63, No. 23. pp. 8516-8522.
@article{504ac30a11084825b11dfdfabfb0297c,
title = "Suppression of Estrogen Biosynthesis by Procyanidin Dimers in Red Wine and Grape Seeds",
abstract = "In breast cancer, in situ estrogen production has been demonstrated to play a major role in promoting tumor growth. Aromatase is the enzyme responsible for the conversion of androgen substrates into estrogens. This enzyme is highly expressed in breast cancer tissue compared with normal breast tissue. A wine extract fraction was recently isolated from red wine that exhibited a potent inhibitory action on aromatase activity. Using UV absorbance analysis, high-performance liquid chromatography profiling, accurate mass-mass spectrometry, and nanospray tandem mass spectrometry, most of the compounds in our red wine fraction were identified as procyanidin B dimers that were shown to be aromatase inhibitors. These chemicals have been found in high levels in grape seeds. Inhibition kinetic analysis on the most potent procyanidin B dimer has revealed that it competes with the binding of the androgen substrate with a Ki value of 6 μM. Because mutations at Asp-309, Ser-378, and His-480 of aromatase significantly affected the binding of the procyanidin B dimer, these active site residues are thought to be important residues that interact with this phytochemical. The in vivo efficacy of procyanidin B dimers was evaluated in an aromatase-transfected MCF-7 breast cancer xenograft model. The procyanidin B dimers were able to reduce androgen-dependent tumor growth, indicating that these chemicals suppress in situ estrogen formation. These in vitro and in vivo studies demonstrated that procyanidin B dimers in red wine and grape seeds could be used as chemopreventive agents against breast cancer by suppressing in situ estrogen biosynthesis.",
author = "Eng, {Elizabeth T.} and JingJing Ye and Dudley Williams and Sheryl Phung and Moore, {Roger E.} and Young, {Mary K.} and Ugis Gruntmanis and Glenn Braunstein and Shiuan Chen",
year = "2003",
month = "12",
day = "1",
language = "English (US)",
volume = "63",
pages = "8516--8522",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "23",

}

TY - JOUR

T1 - Suppression of Estrogen Biosynthesis by Procyanidin Dimers in Red Wine and Grape Seeds

AU - Eng, Elizabeth T.

AU - Ye, JingJing

AU - Williams, Dudley

AU - Phung, Sheryl

AU - Moore, Roger E.

AU - Young, Mary K.

AU - Gruntmanis, Ugis

AU - Braunstein, Glenn

AU - Chen, Shiuan

PY - 2003/12/1

Y1 - 2003/12/1

N2 - In breast cancer, in situ estrogen production has been demonstrated to play a major role in promoting tumor growth. Aromatase is the enzyme responsible for the conversion of androgen substrates into estrogens. This enzyme is highly expressed in breast cancer tissue compared with normal breast tissue. A wine extract fraction was recently isolated from red wine that exhibited a potent inhibitory action on aromatase activity. Using UV absorbance analysis, high-performance liquid chromatography profiling, accurate mass-mass spectrometry, and nanospray tandem mass spectrometry, most of the compounds in our red wine fraction were identified as procyanidin B dimers that were shown to be aromatase inhibitors. These chemicals have been found in high levels in grape seeds. Inhibition kinetic analysis on the most potent procyanidin B dimer has revealed that it competes with the binding of the androgen substrate with a Ki value of 6 μM. Because mutations at Asp-309, Ser-378, and His-480 of aromatase significantly affected the binding of the procyanidin B dimer, these active site residues are thought to be important residues that interact with this phytochemical. The in vivo efficacy of procyanidin B dimers was evaluated in an aromatase-transfected MCF-7 breast cancer xenograft model. The procyanidin B dimers were able to reduce androgen-dependent tumor growth, indicating that these chemicals suppress in situ estrogen formation. These in vitro and in vivo studies demonstrated that procyanidin B dimers in red wine and grape seeds could be used as chemopreventive agents against breast cancer by suppressing in situ estrogen biosynthesis.

AB - In breast cancer, in situ estrogen production has been demonstrated to play a major role in promoting tumor growth. Aromatase is the enzyme responsible for the conversion of androgen substrates into estrogens. This enzyme is highly expressed in breast cancer tissue compared with normal breast tissue. A wine extract fraction was recently isolated from red wine that exhibited a potent inhibitory action on aromatase activity. Using UV absorbance analysis, high-performance liquid chromatography profiling, accurate mass-mass spectrometry, and nanospray tandem mass spectrometry, most of the compounds in our red wine fraction were identified as procyanidin B dimers that were shown to be aromatase inhibitors. These chemicals have been found in high levels in grape seeds. Inhibition kinetic analysis on the most potent procyanidin B dimer has revealed that it competes with the binding of the androgen substrate with a Ki value of 6 μM. Because mutations at Asp-309, Ser-378, and His-480 of aromatase significantly affected the binding of the procyanidin B dimer, these active site residues are thought to be important residues that interact with this phytochemical. The in vivo efficacy of procyanidin B dimers was evaluated in an aromatase-transfected MCF-7 breast cancer xenograft model. The procyanidin B dimers were able to reduce androgen-dependent tumor growth, indicating that these chemicals suppress in situ estrogen formation. These in vitro and in vivo studies demonstrated that procyanidin B dimers in red wine and grape seeds could be used as chemopreventive agents against breast cancer by suppressing in situ estrogen biosynthesis.

UR - http://www.scopus.com/inward/record.url?scp=0346995279&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0346995279&partnerID=8YFLogxK

M3 - Article

VL - 63

SP - 8516

EP - 8522

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 23

ER -