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  3. Zearalenone at environmental levels promoted ER- positive breast cancer cell lines through the hedgehog pathway

Zearalenone at environmental levels promoted ER- positive breast cancer cell lines through the hedgehog pathway

  • Ecotoxicol Environ Saf. 2025 Aug 6:303:118813. doi: 10.1016/j.ecoenv.2025.118813.
Ling Xu 1,  Hui Zhou 1,  Yuting Zhong 1,  Linnan Zhao 1,  Jiangying Qian 1,  Lei Ding 2,  Xuexiu Chang 3,  Christopher Kassotis 4,  Qinghua Cui 5
Affiliations

Affiliations

  • 1 Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China.
  • 2 Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China. Electronic address: dingleiynu@ynu.edu.cn.
  • 3 Yunnan Collaborative Innovation Center for Plateau Lake Ecology and Environmental Health, College of Agronomy and Life Sciences, Kunming University, Kunming 650214, China; Great Lakes Institute for Environmental Research, University of Windsor, Windsor, ON N9B 3P4, Canada. Electronic address: xchang@uwindsor.ca.
  • 4 Department of Pharmacology and Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, United States. Electronic address: christopher.kassotis@wayne.edu.
  • 5 Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China; Yunnan Collaborative Innovation Center for Plateau Lake Ecology and Environmental Health, College of Agronomy and Life Sciences, Kunming University, Kunming 650214, China. Electronic address: cuiqinghua@ynu.edu.cn.
PMID: 40773915 DOI: 10.1016/j.ecoenv.2025.118813
Abstract

Zearalenone (ZEA) has been recognized as a common exogenous nonsteroidal estrogen in environments which possessed a disruptive effect on organisms. Exposure to exogenous estrogen has been revealed to affect breast Cancer development. However, whether ZEA exerts estrogenic effects to influence and cause breast Cancer is poorly documented. We hypothesized that ZEA might act as an estrogen and causative factor in breast Cancer, mainly due to its similarity to naturally occurring estrogens. The aim of this study was to further explore the potential risks of ZEA by comparing the effects of ZEA on the proliferation and invasion of Estrogen receptor (ER) positive/negative breast Cancer cell lines, and to explore its underlying molecular mechanisms. We found that low ZEA concentrations, similar with the real environment, promoted the proliferation, migration and invasion only in ER-positive breast Cancer cells, while high concentrations of ZEA inhibited malignant biological behaviors in both ER positive and negative breast Cancer cells. Consistently, ZEA demonstrated the same biphasic effect (promotion at low dose and inhibition at high dose) on cell stemness and epithelial mesenchymal transition processes, which were further confirmed to be controlled by the Hedgehog pathway. These results highlight the additional health risks posed by ZEA, which warrant greater attention in environmental management.

Keywords

Breast cancer; Cell stemness; Epithelial Mesenchymal Transition; Hedgehog pathway; Zearalenone.

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