PMID- 24894866
OWN - NLM
STAT- MEDLINE
DCOM- 20150218
LR  - 20211021
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 35
IP  - 8
DP  - 2014 Aug
TI  - Resveratrol inhibits estrogen-induced breast carcinogenesis through induction of 
      NRF2-mediated protective pathways.
PG  - 1872-80
LID - 10.1093/carcin/bgu120 [doi]
AB  - The importance of estrogens in the etiology of breast cancer is widely 
      recognized. Estrogen-induced oxidative stress has been implicated in this 
      carcinogenic process. Resveratrol (Res), a natural antioxidant phytoestrogen has 
      chemopreventive effects against a variety of illnesses including cancer. The 
      objective of the present study was to characterize the mechanism(s) of 
      Res-mediated protection against estrogen-induced breast carcinogenesis. Female 
      August Copenhagen Irish rats were treated with 17beta-estradiol (E2), Res and Res + 
      E2 for 8 months. Cotreatment of rats with Res and E2 inhibited E2-mediated 
      proliferative changes in mammary tissues and significantly increased tumor 
      latency and reduced E2-induced breast tumor development. Resveratrol treatment 
      alone or in combination with E2 significantly upregulated expression of nuclear 
      factor erythroid 2-related factor 2 (NRF2) in mammary tissues. Expression of 
      NRF2-regulated antioxidant genes NQO1, SOD3 and OGG1 that are involved in 
      protection against oxidative DNA damage was increased in Res- and Res + 
      E2-treated mammary tissues. Resveratrol also prevented E2-mediated inhibition of 
      detoxification genes AOX1 and FMO1. Inhibition of E2-mediated alterations in NRF2 
      promoter methylation and expression of NRF2 targeting miR-93 after Res treatment 
      indicated Res-mediated epigenetic regulation of NRF2 during E2-induced breast 
      carcinogenesis. Resveratrol treatment also induced apoptosis and inhibited 
      E2-mediated increase in DNA damage in mammary tissues. Increased apoptosis and 
      decreased DNA damage, cell migration, colony and mammosphere formation in Res- 
      and Res + E2-treated MCF-10A cells suggested a protective role of Res against 
      E2-induced mammary carcinogenesis. Small-interfering RNA-mediated silencing of 
      NRF2 inhibited Res-mediated preventive effects on the colony and mammosphere 
      formation. Taken together, these results suggest that Res inhibits E2-induced 
      breast carcinogenesis via induction of NRF2-mediated protective pathways.
CI  - (c) The Author 2014. Published by Oxford University Press. All rights reserved. For 
      Permissions, please email: journals.permissions@oup.com.
FAU - Singh, Bhupendra
AU  - Singh B
AD  - Department of Genetics, School of Medicine, University of Alabama at Birmingham, 
      Birmingham, AL 35294, USA, Institute of Comparative Medicine, Columbia 
      University, New York, NY 10032, USA and Division of Pharmacology and Toxicology, 
      School of Pharmacy and School of Medicine, University of Missouri-Kansas City, 
      Kansas City, MO 64108, USA.
FAU - Shoulson, Rivka
AU  - Shoulson R
AD  - Institute of Comparative Medicine, Columbia University, New York, NY 10032, USA 
      and.
FAU - Chatterjee, Anwesha
AU  - Chatterjee A
AD  - Division of Pharmacology and Toxicology, School of Pharmacy and.
FAU - Ronghe, Amruta
AU  - Ronghe A
AD  - Division of Pharmacology and Toxicology, School of Pharmacy and.
FAU - Bhat, Nimee K
AU  - Bhat NK
AD  - Division of Pharmacology and Toxicology, School of Pharmacy and.
FAU - Dim, Daniel C
AU  - Dim DC
AD  - School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, 
      USA.
FAU - Bhat, Hari K
AU  - Bhat HK
AD  - Division of Pharmacology and Toxicology, School of Pharmacy and bhath@umkc.edu.
LA  - eng
GR  - CA 109551/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140603
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Estrogens)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Stilbenes)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - Animals
MH  - Anticarcinogenic Agents/pharmacology
MH  - Antioxidants
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Transformation, Neoplastic/chemically induced/metabolism/*pathology
MH  - DNA Methylation/drug effects
MH  - Epigenesis, Genetic/drug effects
MH  - Estrogens/*toxicity
MH  - Female
MH  - Humans
MH  - Mammary Neoplasms, Experimental/chemically induced/metabolism/*prevention & 
      control
MH  - NF-E2-Related Factor 2/antagonists & inhibitors/genetics/*metabolism
MH  - RNA, Messenger/genetics
MH  - RNA, Small Interfering/genetics
MH  - Rats, Inbred ACI
MH  - Rats, Inbred Strains
MH  - Real-Time Polymerase Chain Reaction
MH  - Resveratrol
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*drug effects
MH  - Stilbenes/*pharmacology
MH  - Tumor Cells, Cultured
PMC - PMC4123650
EDAT- 2014/06/05 06:00
MHDA- 2015/02/19 06:00
PMCR- 2015/08/01
CRDT- 2014/06/05 06:00
PHST- 2014/06/05 06:00 [entrez]
PHST- 2014/06/05 06:00 [pubmed]
PHST- 2015/02/19 06:00 [medline]
PHST- 2015/08/01 00:00 [pmc-release]
AID - bgu120 [pii]
AID - 10.1093/carcin/bgu120 [doi]
PST - ppublish
SO  - Carcinogenesis. 2014 Aug;35(8):1872-80. doi: 10.1093/carcin/bgu120. Epub 2014 Jun 
      3.