17β-estradiol at low concentrations attenuates the efficacy of tamoxifen in breast cancer therapy

Zhixiang Xu; Xianyao Zheng; Xueshan Xia; Xiaoxia Wang; Nao Luo; Bin Huang; Xuejun Pan

doi:10.1016/j.envpol.2019.113228

17β-estradiol at low concentrations attenuates the efficacy of tamoxifen in breast cancer therapy

Environ Pollut. 2019 Dec;255(Pt 2):113228. doi: 10.1016/j.envpol.2019.113228. Epub 2019 Sep 20.

Authors

Zhixiang Xu¹, Xianyao Zheng², Xueshan Xia³, Xiaoxia Wang², Nao Luo², Bin Huang², Xuejun Pan⁴

Affiliations

¹ Faculty of Environmental Science & Engineering, Kunming University of Science and Technology, Kunming, 650500, China; Faculty of Life Science & Technology, Kunming University of Science and Technology, Kunming, 650500, China.
² Faculty of Environmental Science & Engineering, Kunming University of Science and Technology, Kunming, 650500, China.
³ Faculty of Life Science & Technology, Kunming University of Science and Technology, Kunming, 650500, China.
⁴ Faculty of Environmental Science & Engineering, Kunming University of Science and Technology, Kunming, 650500, China. Electronic address: xjpan@kust.edu.cn.

PMID: 31563769
DOI: 10.1016/j.envpol.2019.113228

Abstract

Tamoxifen has been applied widely in the treatment of estrogen receptor (ER)-positive breast cancer. The impact of low concentrations of 17β-estradiol (E2) (a pervasive environmental pollutant) on its effectiveness was studied in vitro using an MCF-7 cell line. Cell proliferation, migration, invasion, and apoptosis were studied along with cell cycle progression, reactive oxygen species generation and mitochondrial membrane potentials repression. The signaling pathways involved were identified. Typical concentrations of E2 in the environment (10^-10 to 10^-8 M) were observed to promote cell growth and protect MCF-7 cells from tamoxifen's cytotoxicity. Cell migration, invasion, cell cycle progression and apoptosis all involved in reducing tamoxifen's cytotoxicity. E2 at environmental concentrations induced PI3K/Akt and MAPK/ERK signal transduction through the estrogen receptor pathways to affect cell proliferation. Taken together, the results explain how E2 in the environment may attenuate the efficacy of tamoxifen in ER-positive breast cancer therapy. They provide considerable support for E2's adverse effects on human health and cancer management.

Keywords: 17β-estradiol; Cytotoxicity; Endocrine resistance; Estrogen receptors; Tamoxifen.

MeSH terms

Breast Neoplasms / drug therapy
Breast Neoplasms / metabolism*
Cell Division / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Estradiol / toxicity*
Female
Humans
MCF-7 Cells
Phosphatidylinositol 3-Kinases / metabolism
Receptors, Estrogen / metabolism
Signal Transduction / drug effects
Tamoxifen / therapeutic use*

Substances

Receptors, Estrogen
Tamoxifen
Estradiol