Dissecting the prevention of estrogen-dependent breast carcinogenesis through Nrf2-dependent and independent mechanisms

Aldo Giudice, Antonio Barbieri, Sabrina Bimonte, Marco Cascella, Arturo Cuomo, Anna Crispo, Giovanni D'arena, Massimiliano Galdiero, Maria Elena Della Pepa, Gerardo Botti, Michele Caraglia, Mario Capunzo, Claudio Arra, Maurizio Montella

Research output: Contribution to journalReview article

Abstract

Breast cancer is the most common malignancy among women worldwide. Various studies indicate that prolonged exposure to elevated levels of estrogens is associated with development of breast cancer. Both estrogen receptor-dependent and independent mechanisms can contribute to the carcinogenic effects of estrogens. Among them, the oxidative metabolism of estrogens plays a key role in the initiation of estradiol-induced breast cancer by generation of reactive estrogen quinones as well as the associated formation of oxygen free radicals. These genotoxic metabolites can react with DNA to form unstable DNA adducts which generate mutations leading to the initiation of breast cancer. A variety of endogenous and exogenous factors can alter estrogen homeostasis and generate genotoxic metabolites. The use of specific phytochemicals and dietary supplements can inhibit the risk of breast cancer not only by the modulation of several estrogen-activating enzymes (CYP19, CYP1B1) but also through the induction of various cytoprotective enzymes (eg, SOD3, NQO1, glutathione S-transferases, OGG-1, catechol-O-methyltransferases, CYP1B1A, etc.) that reestablish the homeostatic balance of estrogen metabolism via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent and independent mechanisms.

Original languageEnglish
Pages (from-to)4937-4953
Number of pages17
JournalOncoTargets and Therapy
Volume12
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Estrogens
Carcinogenesis
Breast
Breast Neoplasms
Catechol O-Methyltransferase
Quinones
DNA Adducts
Phytochemicals
Dietary Supplements
Glutathione Transferase
Estrogen Receptors
Free Radicals
Estradiol
Reactive Oxygen Species
Homeostasis
Mutation
DNA
Enzymes
Neoplasms

Keywords

  • Breast carcinogenesis
  • Depurinating estrogen-DNA adducts
  • Dietary phytochemicals
  • Nuclear factor erythroid 2-related factor 2
  • Reactive estrogen quinones

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

Cite this

Dissecting the prevention of estrogen-dependent breast carcinogenesis through Nrf2-dependent and independent mechanisms. / Giudice, Aldo; Barbieri, Antonio; Bimonte, Sabrina; Cascella, Marco; Cuomo, Arturo; Crispo, Anna; D'arena, Giovanni; Galdiero, Massimiliano; Pepa, Maria Elena Della; Botti, Gerardo; Caraglia, Michele; Capunzo, Mario; Arra, Claudio; Montella, Maurizio.

In: OncoTargets and Therapy, Vol. 12, 01.01.2019, p. 4937-4953.

Research output: Contribution to journalReview article

@article{8a171c4776944d9ba54f2699fadb21b9,
title = "Dissecting the prevention of estrogen-dependent breast carcinogenesis through Nrf2-dependent and independent mechanisms",
abstract = "Breast cancer is the most common malignancy among women worldwide. Various studies indicate that prolonged exposure to elevated levels of estrogens is associated with development of breast cancer. Both estrogen receptor-dependent and independent mechanisms can contribute to the carcinogenic effects of estrogens. Among them, the oxidative metabolism of estrogens plays a key role in the initiation of estradiol-induced breast cancer by generation of reactive estrogen quinones as well as the associated formation of oxygen free radicals. These genotoxic metabolites can react with DNA to form unstable DNA adducts which generate mutations leading to the initiation of breast cancer. A variety of endogenous and exogenous factors can alter estrogen homeostasis and generate genotoxic metabolites. The use of specific phytochemicals and dietary supplements can inhibit the risk of breast cancer not only by the modulation of several estrogen-activating enzymes (CYP19, CYP1B1) but also through the induction of various cytoprotective enzymes (eg, SOD3, NQO1, glutathione S-transferases, OGG-1, catechol-O-methyltransferases, CYP1B1A, etc.) that reestablish the homeostatic balance of estrogen metabolism via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent and independent mechanisms.",
keywords = "Breast carcinogenesis, Depurinating estrogen-DNA adducts, Dietary phytochemicals, Nuclear factor erythroid 2-related factor 2, Reactive estrogen quinones",
author = "Aldo Giudice and Antonio Barbieri and Sabrina Bimonte and Marco Cascella and Arturo Cuomo and Anna Crispo and Giovanni D'arena and Massimiliano Galdiero and Pepa, {Maria Elena Della} and Gerardo Botti and Michele Caraglia and Mario Capunzo and Claudio Arra and Maurizio Montella",
year = "2019",
month = "1",
day = "1",
doi = "10.2147/OTT.S183192",
language = "English",
volume = "12",
pages = "4937--4953",
journal = "OncoTargets and Therapy",
issn = "1178-6930",
publisher = "Dove Medical Press Ltd.",

}

TY - JOUR

T1 - Dissecting the prevention of estrogen-dependent breast carcinogenesis through Nrf2-dependent and independent mechanisms

AU - Giudice, Aldo

AU - Barbieri, Antonio

AU - Bimonte, Sabrina

AU - Cascella, Marco

AU - Cuomo, Arturo

AU - Crispo, Anna

AU - D'arena, Giovanni

AU - Galdiero, Massimiliano

AU - Pepa, Maria Elena Della

AU - Botti, Gerardo

AU - Caraglia, Michele

AU - Capunzo, Mario

AU - Arra, Claudio

AU - Montella, Maurizio

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Breast cancer is the most common malignancy among women worldwide. Various studies indicate that prolonged exposure to elevated levels of estrogens is associated with development of breast cancer. Both estrogen receptor-dependent and independent mechanisms can contribute to the carcinogenic effects of estrogens. Among them, the oxidative metabolism of estrogens plays a key role in the initiation of estradiol-induced breast cancer by generation of reactive estrogen quinones as well as the associated formation of oxygen free radicals. These genotoxic metabolites can react with DNA to form unstable DNA adducts which generate mutations leading to the initiation of breast cancer. A variety of endogenous and exogenous factors can alter estrogen homeostasis and generate genotoxic metabolites. The use of specific phytochemicals and dietary supplements can inhibit the risk of breast cancer not only by the modulation of several estrogen-activating enzymes (CYP19, CYP1B1) but also through the induction of various cytoprotective enzymes (eg, SOD3, NQO1, glutathione S-transferases, OGG-1, catechol-O-methyltransferases, CYP1B1A, etc.) that reestablish the homeostatic balance of estrogen metabolism via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent and independent mechanisms.

AB - Breast cancer is the most common malignancy among women worldwide. Various studies indicate that prolonged exposure to elevated levels of estrogens is associated with development of breast cancer. Both estrogen receptor-dependent and independent mechanisms can contribute to the carcinogenic effects of estrogens. Among them, the oxidative metabolism of estrogens plays a key role in the initiation of estradiol-induced breast cancer by generation of reactive estrogen quinones as well as the associated formation of oxygen free radicals. These genotoxic metabolites can react with DNA to form unstable DNA adducts which generate mutations leading to the initiation of breast cancer. A variety of endogenous and exogenous factors can alter estrogen homeostasis and generate genotoxic metabolites. The use of specific phytochemicals and dietary supplements can inhibit the risk of breast cancer not only by the modulation of several estrogen-activating enzymes (CYP19, CYP1B1) but also through the induction of various cytoprotective enzymes (eg, SOD3, NQO1, glutathione S-transferases, OGG-1, catechol-O-methyltransferases, CYP1B1A, etc.) that reestablish the homeostatic balance of estrogen metabolism via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent and independent mechanisms.

KW - Breast carcinogenesis

KW - Depurinating estrogen-DNA adducts

KW - Dietary phytochemicals

KW - Nuclear factor erythroid 2-related factor 2

KW - Reactive estrogen quinones

UR - http://www.scopus.com/inward/record.url?scp=85069856907&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069856907&partnerID=8YFLogxK

U2 - 10.2147/OTT.S183192

DO - 10.2147/OTT.S183192

M3 - Review article

VL - 12

SP - 4937

EP - 4953

JO - OncoTargets and Therapy

JF - OncoTargets and Therapy

SN - 1178-6930

ER -