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Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways

Authors Tan W, Pan M, Liu H, Tian H, Ye Q, Liu H

Received 6 April 2017

Accepted for publication 15 June 2017

Published 13 July 2017 Volume 2017:10 Pages 3467—3474

DOI https://doi.org/10.2147/OTT.S139009

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ashok Kumar Pandurangan

Peer reviewer comments 3

Editor who approved publication: Dr William Cho

Weiwei Tan,1,* Meihong Pan,1,* Hui Liu,1 Hequn Tian,1 Qing Ye,1 Hongda Liu2

1Department of Traditional Chinese Medicine, Yidu Central Hospital of Weifang, Weifang, Shandong, China; 2Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, Shandong, China

*These authors contributed equally to this work

Abstract: Ergosterol peroxide (EP), a sterol derived from medicinal mushrooms, has been reported to exert antitumor activity in several tumor types. However, the role of EP toward ovarian cancer cells has not been investigated. In this study, we analyzed the cytotoxicity of EP in various cell lines representing high-grade serous ovarian cancer and low-grade serous ovarian cancer, respectively. Although EP showed no significant inhibition of the viability of normal ovarian surface epithelial cells, it impaired the proliferation and invasion capacities of tumor cells in a dose-dependent manner. We further figured out key modulators involved in its antitumor effects by quantitative reverse transcription polymerase chain reaction, ELISA, and Western blot. The nuclear β-catenin was down-regulated upon EP treatment, subsequently reducing the Cyclin D1 and c-Myc expression levels. Meanwhile, the protein level of protein tyrosine phosphatase SHP2 was up-regulated in EP treated cells, whereas Src kinase activity was inhibited. Both activation of SHP2 phosphatase and inhibition of Src kinase decreased the phosphorylation level of transducer and activator of STAT3 protein, which was implicated in oncogenesis. On the other hand, EP remarkably inhibited the expression and secretion of VEGF-C, implying its involvement in counteracting tumor angiogenesis. Moreover, EP treatment showed comparable cytotoxic effect with β-catenin knock-down or STAT3 inhibition. Taken together, our results demonstrated that EP showed antitumor effects toward ovarian cancer cells through both β-catenin and STAT3 signaling pathways, making it a promising candidate for drug development.

Keywords: β-catenin, ergosterol peroxide, ovarian cancer, STAT3

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