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In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product From Cucumber

Cucurbitacin C (CuC), a novel analogue of triterpenoids cucurbitacins, confers a bitter taste in cucumber. Genes and signaling pathways responsive for biosynthesis of CuC have been identified in the recent years. In the present study, we explored the anti-cancer effects of CuC against human cancers...

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Autores principales: Wu, Dinglan, Wang, Zhu, Lin, Muqi, Shang, Yi, Wang, Fei, Zhou, JiaYi, Zhang, Xiantong, Luo, Xiaomin, Huang, Weiren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857091/
https://www.ncbi.nlm.nih.gov/pubmed/31780930
http://dx.doi.org/10.3389/fphar.2019.01287
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author Wu, Dinglan
Wang, Zhu
Lin, Muqi
Shang, Yi
Wang, Fei
Zhou, JiaYi
Wang, Fei
Zhang, Xiantong
Luo, Xiaomin
Huang, Weiren
author_facet Wu, Dinglan
Wang, Zhu
Lin, Muqi
Shang, Yi
Wang, Fei
Zhou, JiaYi
Wang, Fei
Zhang, Xiantong
Luo, Xiaomin
Huang, Weiren
author_sort Wu, Dinglan
collection PubMed
description Cucurbitacin C (CuC), a novel analogue of triterpenoids cucurbitacins, confers a bitter taste in cucumber. Genes and signaling pathways responsive for biosynthesis of CuC have been identified in the recent years. In the present study, we explored the anti-cancer effects of CuC against human cancers in vitro and in vivo. CuC inhibited proliferation and clonogenic potential of multiple cancer cells in a dose-dependent manner. Low-dose CuC treatment induced cell cycle arrest at G1 or G2/M stage in different cancer lines, whereas high-dose treatment of CuC caused apoptosis in cancer cells. PI3K-Akt signaling pathway was found to be one of the major pathways involved in CuC-induced cell growth arrest and apoptosis by RNA-Seq and Western blotting. Mechanistic dissection further confirmed that CuC effectively inhibited the Akt signaling by inhibition of Akt phosphorylation at Ser473. In vivo CuC treatment (0.1 mg/kg body weight) effectively inhibited growth of cancer cell-derived xenograft tumors in athymic nude mice and caused significant apoptosis. Our findings for the first time demonstrated the potential therapeutic significance of CuC against human cancers.
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spelling pubmed-68570912019-11-28 In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product From Cucumber Wu, Dinglan Wang, Zhu Lin, Muqi Shang, Yi Wang, Fei Zhou, JiaYi Wang, Fei Zhang, Xiantong Luo, Xiaomin Huang, Weiren Front Pharmacol Pharmacology Cucurbitacin C (CuC), a novel analogue of triterpenoids cucurbitacins, confers a bitter taste in cucumber. Genes and signaling pathways responsive for biosynthesis of CuC have been identified in the recent years. In the present study, we explored the anti-cancer effects of CuC against human cancers in vitro and in vivo. CuC inhibited proliferation and clonogenic potential of multiple cancer cells in a dose-dependent manner. Low-dose CuC treatment induced cell cycle arrest at G1 or G2/M stage in different cancer lines, whereas high-dose treatment of CuC caused apoptosis in cancer cells. PI3K-Akt signaling pathway was found to be one of the major pathways involved in CuC-induced cell growth arrest and apoptosis by RNA-Seq and Western blotting. Mechanistic dissection further confirmed that CuC effectively inhibited the Akt signaling by inhibition of Akt phosphorylation at Ser473. In vivo CuC treatment (0.1 mg/kg body weight) effectively inhibited growth of cancer cell-derived xenograft tumors in athymic nude mice and caused significant apoptosis. Our findings for the first time demonstrated the potential therapeutic significance of CuC against human cancers. Frontiers Media S.A. 2019-11-08 /pmc/articles/PMC6857091/ /pubmed/31780930 http://dx.doi.org/10.3389/fphar.2019.01287 Text en Copyright © 2019 Wu, Wang, Lin, Shang, Wang, Zhou, Wang, Zhang, Luo and Huang http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wu, Dinglan
Wang, Zhu
Lin, Muqi
Shang, Yi
Wang, Fei
Zhou, JiaYi
Wang, Fei
Zhang, Xiantong
Luo, Xiaomin
Huang, Weiren
In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product From Cucumber
title In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product From Cucumber
title_full In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product From Cucumber
title_fullStr In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product From Cucumber
title_full_unstemmed In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product From Cucumber
title_short In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product From Cucumber
title_sort in vitro and in vivo antitumor activity of cucurbitacin c, a novel natural product from cucumber
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857091/
https://www.ncbi.nlm.nih.gov/pubmed/31780930
http://dx.doi.org/10.3389/fphar.2019.01287
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