PMID- 30009768
OWN - NLM
STAT- MEDLINE
DCOM- 20190404
LR  - 20190404
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 155
DP  - 2018 Sep
TI  - Resveratrol represses estrogen-induced mammary carcinogenesis through 
      NRF2-UGT1A8-estrogen metabolic axis activation.
PG  - 252-263
LID - S0006-2952(18)30274-0 [pii]
LID - 10.1016/j.bcp.2018.07.006 [doi]
AB  - Estrogen plays a pivotal role in the pathological development of breast cancer. 
      Resveratrol has chemo-preventive effects against breast cancer, whereas, the 
      mechanism of antitumor activities of resveratrol remains unanswered. In this 
      study, we showed that estrogen homeostasis profile was disturbed in both breast 
      cancer patients and in experimental breast cancer model rats, with carcinogenic 
      catechol estrogens significantly accumulated in the mammary tissues. 
      UDP-glucuronosyltransferase 1A8 (UGT1A8) is an important phase II 
      drug-metabolizing enzymes which involved in the metabolism of catechol estrogens. 
      Here we found that the mammary nuclear factor erythroid 2-related factor 2 (NRF2) 
      - UGT1A8 signaling was down-regulated in breast cancer rats, whereas treatment 
      with resveratrol could upregulate the expression of NRF2 and UGT1A8, accelerate 
      metabolic elimination of catechol estrogens, inhibit estrogen-induced DNA damage 
      and suppress the pathological development of breast cancer. In addition, 
      luciferase reporter assay suggested that resveratrol activated the expression of 
      UGT1A8 by up-regulating the transcriptional activity of NRF2. Small-interfering 
      RNA-mediated silencing of NRF2 abolished resveratrol-mediated preventive effects 
      indicated that the antitumor effect of resveratrol is based on 
      NRF2-UGT1A8-estrogen metabolism axis. Taken together, we established the 
      resveratrol regulating potential on estrogen homeostasis based on NRF2-UGT1A8 
      signaling pathway, and also provided a novel link between estrogen 
      glucuronidation metabolism and breast cancer pathological development.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Zhou, Xueyan
AU  - Zhou X
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Zhao, Yun
AU  - Zhao Y
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Wang, Juan
AU  - Wang J
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Wang, Xi
AU  - Wang X
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Chen, Chunxia
AU  - Chen C
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Yin, Di
AU  - Yin D
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Zhao, Feng
AU  - Zhao F
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Yin, Jiale
AU  - Yin J
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Guo, Meng
AU  - Guo M
AD  - Department of Thyroid and Breast Surgery, The Affiliated Hospital of Xuzhou 
      Medical University, Xuzhou, China.
FAU - Zhang, Longzhen
AU  - Zhang L
AD  - Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, China.
FAU - Du, Lei
AU  - Du L
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China.
FAU - Zhang, Bei
AU  - Zhang B
AD  - Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou Clinical 
      School of Xuzhou Medical University, Xuzhou, China. Electronic address: 
      bettyzhang10@163.com.
FAU - Yin, Xiaoxing
AU  - Yin X
AD  - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical 
      University, Xuzhou, China. Electronic address: yinxx@xzhmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180720
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Estrogens)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - EC 2.4.1.17 (UDP-glucuronosyltransferase, UGT1A8)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/pharmacology/*therapeutic use
MH  - Breast Neoplasms/drug therapy/*metabolism
MH  - Cell Line
MH  - Estrogens/analysis/*metabolism
MH  - Female
MH  - Glucuronosyltransferase/analysis/*metabolism
MH  - Humans
MH  - NF-E2-Related Factor 2/analysis/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Resveratrol/pharmacology/*therapeutic use
MH  - Tandem Mass Spectrometry/methods
OTO - NOTNLM
OT  - Breast cancer
OT  - Estrogen
OT  - Nuclear factor erythroid 2-related factor 2 (NRF2)
OT  - Resveratrol
OT  - UDP-Glucuronosyltransferase (UGT)
EDAT- 2018/07/17 06:00
MHDA- 2019/04/05 06:00
CRDT- 2018/07/17 06:00
PHST- 2018/05/03 00:00 [received]
PHST- 2018/07/11 00:00 [accepted]
PHST- 2018/07/17 06:00 [pubmed]
PHST- 2019/04/05 06:00 [medline]
PHST- 2018/07/17 06:00 [entrez]
AID - S0006-2952(18)30274-0 [pii]
AID - 10.1016/j.bcp.2018.07.006 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2018 Sep;155:252-263. doi: 10.1016/j.bcp.2018.07.006. Epub 
      2018 Jul 20.