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  2. Benzophenone-1 induced aberrant proliferation and metastasis of ovarian cancer cells via activated ERα and Wnt/β-catenin signaling pathways

Benzophenone-1 induced aberrant proliferation and metastasis of ovarian cancer cells via activated ERα and Wnt/β-catenin signaling pathways

  • Environ Pollut. 2022 Jan 1;292(Pt B):118370. doi: 10.1016/j.envpol.2021.118370.
Xujun Liu 1 Tingjie Zhan 1 Yuchen Gao 1 Shixuan Cui 1 Weiping Liu 1 Chunlong Zhang 2 Shulin Zhuang 3
Affiliations

Affiliations

  • 1 Key Laboratory of Environment Remediation and Ecological Health, Ministry of Education, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058, China.
  • 2 Department of Environmental Sciences, University of Houston-Clear Lake, 2700 Bay Area Boulevard, Houston, TX, 77058, United States.
  • 3 Key Laboratory of Environment Remediation and Ecological Health, Ministry of Education, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058, China. Electronic address: [email protected].
Abstract

Benzophenone-1 (BP-1) belongs to personal care product-related contaminants of emerging concern and has been recently reported to induce xenoestrogenic effects. However, the underlying mechanisms leading to the activation of target receptors and subsequent various adverse outcomes remain unclear, which is beneficial to safety and health risk assessment of benzophenone-type ultraviolet filters with their widespread occurrence. Herein, we investigated disrupting effects of BP-1 at environmentally relevant concentrations (10-9-10-6 M) on Estrogen Receptor (ER) α-associated signaling pathways. Molecular dynamics simulations together with yeast-based assays revealed the steady binding of BP-1 to ERα ligand binding domain (LBD) and hence the observed agonistic activity. BP-1 triggered interaction between ERα and β-catenin in human SKOV3 ovarian Cancer cells and caused translocation of β-catenin from the cytoplasm to the nucleus, leading to aberrant activation of Wnt/β-catenin. BP-1 consequently induced dissemination of SKOV3 via regulating epithelial-mesenchymal transitions (EMT) biomarkers including minimally downregulating ZO-1 gene to 78.0 ± 10.1% and maximally upregulating MMP9 gene to 144.1 ± 29.7% and promoted 1.03-1.83 fold proliferation, migration and invasion of SKOV3. We provide the first evidence that the BP-1 activated ERα triggers crosstalk between ERα and Wnt/β-catenin pathway, leading to the abnormal stimulation and progression of SKOV3 Cancer cells.

Keywords

Cell migration and invasion; Estrogenic disruption; Health risk; Ovarian cancer; Personal care product.

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