Antitumor effects of aconitine in A2780 cells via estrogen receptor β‑mediated apoptosis, DNA damage and migration

Wang,Xiuying; Lin,Yuanyuan; Zheng,Yi

doi:10.3892/mmr.2020.11322

Antitumor effects of aconitine in A2780 cells via estrogen receptor β‑mediated apoptosis, DNA damage and migration

Authors:
- Xiuying Wang
- Yuanyuan Lin
- Yi Zheng
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Affiliations: Pharmaceutical Preparation Section, People's Hospital of Weifang High‑tech Zone, Weifang, Shangdong 261205, P.R. China, Department of Nursing, Weifang Hospital of Traditional Chinese Medicine, Weifang, Shandong 261031, P.R. China, Department of Medical Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261041, P.R. China
Published online on: July 10, 2020 https://doi.org/10.3892/mmr.2020.11322
Pages: 2318-2328
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ovarian cancer (OVCA) is the deadliest type of malignant gynecological disease, and previous studies have demonstrated that estrogen receptor β (ERβ) serves important roles in this disease. Aconitine, a toxin produced by the Aconitum plant, displays potent effects against cancers. The aim of the study was to investigate the pharmacological activities and mechanisms of aconitum on OVCA. In the present study, the activity of aconitine in the human OVCA A2780 cell line was investigated. The results revealed that aconitine suppressed cell viability, colony formation and motility. Terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling, mitochondria membrane potential and comet assays showed that aconitine induced mitochondria apoptosis and DNA damage in A2780 cells. Investigation of the mechanism revealed that a high expression of ERβ and prolyl hydroxylase 2 was detected after aconitine treatment, and aconitine significantly suppressed the expression of vascular endothelial growth factor and hypoxia‑inducible factor 1α to activate ERβ signaling. Moreover, the expression levels of p53, Bax, apoptotic peptidase activating factor 1, cytochrome C, cleaved caspase‑3/9 and cleaved poly (ADP‑ribose) polymerase were upregulated, and the expression levels of Bcl‑2, Bcl‑xl and phosphorylated ATM serine/threonine kinase were downregulated by aconitine. Interestingly, aconitine also markedly downregulated the expression of matrix metalloproteinase 2 (MMP2) and MMP9, which are associated with tumor invasion. In addition, a molecular docking assay revealed that aconitine exerted strong affinity towards ERβ mainly through hydrogen bonding and hydrophobic effects. Collectively, these results suggested that aconitine suppressed OVCA cell growth by adjusting ERβ‑mediated apoptosis, DNA damage and migration, which should be considered a potential option for the future treatment of OVCA.

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