ESC-3 induces apoptosis of human ovarian carcinomas through Wnt/β-catenin and Notch signaling in vitro and in vivo

Fu,Qi-Rui; Song,Wei; Deng,Yi-Tao; Li,Hua-Liang; Mao,Xiao-Mei; Lin,Chen-Lu; Zheng,Ya-Hui; Chen,Shu-Ming; Chen,Qiong-Hua; Chen,Qing-Xi

doi:10.3892/ijo.2016.3773

ESC-3 induces apoptosis of human ovarian carcinomas through Wnt/β-catenin and Notch signaling in vitro and in vivo

Authors:
- Qi-Rui Fu
- Wei Song
- Yi-Tao Deng
- Hua-Liang Li
- Xiao-Mei Mao
- Chen-Lu Lin
- Ya-Hui Zheng
- Shu-Ming Chen
- Qiong-Hua Chen
- Qing-Xi Chen
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Affiliations: State Key Laboratory of Cellular Stress Biology, Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P.R. China, College of Life Science and Engineering, Henan University of Urban Construction, Ping Dingshan, Henan 467036, P.R. China, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
Published online on: November 18, 2016 https://doi.org/10.3892/ijo.2016.3773
Pages: 241-251

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Abstract

Apoptosis, programmed cell death under physiological or pathological conditions, plays a critical role in the tissue homeostasis of eukaryotes. It is desirable to prevent the occurrence and metastasis of cancer through inducing apoptosis. Our previous study demonstrated that apoptosis could be induced by extract from crocodile in human cholangiocarcinoma. ESC-3, a novel cytotoxic compound isolated from the extract induced apoptosis in Mz-ChA-1 cells via the mitochondria-dependent pathway in a dose-dependent manner. In this study, ESC-3 significantly inhibited the proliferation of A2780 cells and arrested the cells at G2/M phase. After exposure to ESC-3, A2780 cells displayed typical morphological changes and the ability of colony-forming was remarkably inhibited. ESC-3 could significantly upregulate the expression of Bax proteins while Bcl-2 protein remained unchanged, resulting in the elevation of Bax/Bcl-2 ratio, which usually could induce apoptosis. The critical protein of Wnt signaling (β-catenin) was significantly downregulated, whereas Hes1, the downstream protein of Notch signaling, was remarkably attenuated through upregulating the expression of P53. In addition, xenograft models demonstrated that ESC-3 effectively suppressed the growth of OvCa tumors (T/C=42%). Western blot analysis of PCNA and VEGF confirmed that ESC-3 could inhibit the growth and metastasis of OvCa tumors. In conclusion, apoptosis could be induced by ESC-3 through Wnt/β-catenin and Notch signaling in vitro and in vivo, and might have therapeutic potential for the treatment of human OvCa.

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