Open AccessAlantolactone promotes ER stress‐mediated apoptosis by inhibition of TrxR1 in triple‐negative breast cancer cell lines and in a mouse model
Author(s) -
Yin Changtian,
Dai Xuanxuan,
Huang Xiangjie,
Zhu Wangyu,
Chen Xi,
Zhou Qiulin,
Wang Canwei,
Zhao Chengguang,
Zou Peng,
Liang Guang,
Rajamanickam Vinothkumar,
Wang Ouchen,
Zhang Xiaohua,
Cui Ri
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14139
Subject(s) - triple negative breast cancer , cancer research , apoptosis , unfolded protein response , gene knockdown , in vivo , reactive oxygen species , breast cancer , viability assay , cancer , chemistry , biology , medicine , microbiology and biotechnology , biochemistry
Abstract Triple‐negative breast cancer (TNBC) is a subtype of breast cancer with poor clinical outcome and currently no effective targeted therapies are available. Alantolactone (ATL), a sesquiterpene lactone, has been shown to have potential anti‐tumour activity against various cancer cells. However, the underlying mechanism and therapeutic effect of ATL in the TNBC are largely unknown. In the present study, we found that ATL suppresses TNBC cell viability by reactive oxygen species (ROS) accumulation and subsequent ROS‐dependent endoplasmic reticulum (ER) stress both in vitro and in vivo. Thioredoxin reductase 1 (TrxR1) expression and activity of were significantly up‐regulated in the TNBC tissue specimens compare to the normal adjacent tissues. Further analyses showed that ATL inhibits the activity of TrxR1 both in vitro and in vivo in TNBC and knockdown of TrxR1 in TNBC cells sensitized ATL‐induced cell apoptosis and ROS increase. These results will provide pre‐clinical evidences that ATL could be a potential therapeutic agent against TNBC by promoting ROS‐ER stress‐mediated apoptosis through partly targeting TrxR1.