Oncotarget

Research Papers:

Chemopreventive effects of atractylenolide II on mammary tumorigenesis via activating Nrf2-ARE pathway

Ting Wang, Fangyi Long, Xiqian Zhang, Yujie Yang, Xuehua Jiang and Ling Wang _

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Oncotarget. 2017; 8:77500-77514. https://doi.org/10.18632/oncotarget.20546

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Abstract

Ting Wang1,2,*, Fangyi Long3,*, Xiqian Zhang1, Yujie Yang1, Xuehua Jiang1 and Ling Wang1

1Department of Clinical Pharmacy and Pharmacy Administration, Key Laboratory of Drug Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, Sichuan, China

2Department of Pharmacy, Sichuan Cancer Hospital & Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China

3Department of Pharmacy, Sichuan Provincial Hospital for Women and Children, Women and Children’s Hospital of Chengdu Medical College, Chengdu Medical College, Chengdu 610041, China

*These authors have contributed equally to this work

Correspondence to:

Ling Wang, email: [email protected]

Keywords: breast cancer, atractylenolide II, nuclear factor (erythroid-derived 2)-like 2, anti-oxidative response element, chemoprevention

Received: July 03, 2017     Accepted: August 04, 2017     Published: August 24, 2017

ABSTRACT

In the studies of chemoprevention, the Nrf2-ARE signaling pathway has received widespread attention due to its anti-inflammatory and anti-oxidation effects. Our previous study indicated that atractylenolide II, which is an active component of Atractylodes macrocephala Koidz, is a potential activator of Nrf2-ARE signaling pathway. In this study, we observed that atractylenolide II significantly increased Nrf2 expressing, nuclear translocation and the expression of its downstream detoxifying enzymes, thus decreasing 17β-Estradiol induced malignant transformation in MCF 10A cells, and we found that atractylenolide II acted through JNK/ERK-Nrf2-ARE pathway. Furthermore, atractylenolide II significantly reduced N-Nitroso-N-methylurea induced tumor incidence, multiplicity and volume, with activation of Nrf2-ARE pathway and decreased inflammation and oxidative stress in rat mammary tissue. Collectively, our results suggested that atractylenolide II could protect against mammary tumorigenesis both in vivo and in vitro via activating Nrf2-ARE signaling pathway, which supported atractylenolide II as a novel chemopreventive agent of breast cancer.


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