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Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways

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 representi...

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Autores principales: Tan, Weiwei, Pan, Meihong, Liu, Hui, Tian, Hequn, Ye, Qing, Liu, Hongda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518915/
https://www.ncbi.nlm.nih.gov/pubmed/28761355
http://dx.doi.org/10.2147/OTT.S139009
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author Tan, Weiwei
Pan, Meihong
Liu, Hui
Tian, Hequn
Ye, Qing
Liu, Hongda
author_facet Tan, Weiwei
Pan, Meihong
Liu, Hui
Tian, Hequn
Ye, Qing
Liu, Hongda
author_sort Tan, Weiwei
collection PubMed
description 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.
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spelling pubmed-55189152017-07-31 Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways Tan, Weiwei Pan, Meihong Liu, Hui Tian, Hequn Ye, Qing Liu, Hongda Onco Targets Ther Original Research 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. Dove Medical Press 2017-07-13 /pmc/articles/PMC5518915/ /pubmed/28761355 http://dx.doi.org/10.2147/OTT.S139009 Text en © 2017 Tan et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Tan, Weiwei
Pan, Meihong
Liu, Hui
Tian, Hequn
Ye, Qing
Liu, Hongda
Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways
title Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways
title_full Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways
title_fullStr Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways
title_full_unstemmed Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways
title_short Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways
title_sort ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518915/
https://www.ncbi.nlm.nih.gov/pubmed/28761355
http://dx.doi.org/10.2147/OTT.S139009
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