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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doaj-49e287bf4647488ca4e759b13479ae682020-11-25T01:18:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-11-011010.3389/fphar.2019.01287471751In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product From CucumberDinglan Wu0Zhu Wang1Muqi Lin2Yi Shang3Fei Wang4JiaYi Zhou5Fei Wang6Xiantong Zhang7Xiaomin Luo8Weiren Huang9Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University, Shenzhen, ChinaDepartment of Urology, People’s Hospital of Longhua Shenzhen, Southern Medical University, Shenzhen, ChinaSchool of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, ChinaAgricultural Genome Institute at Shenzhen, Chinese Academy of Agricultural Science, Shenzhen, ChinaDepartment of Urology, The Hospital of Hainan Province, Haikou, ChinaShenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University, Shenzhen, ChinaShenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University, Shenzhen, ChinaShenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University, Shenzhen, ChinaShenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University, Shenzhen, ChinaDepartment of Urology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, International Cancer Center, Shenzhen University School of Medicine, Shenzhen, ChinaCucurbitacin 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.https://www.frontiersin.org/article/10.3389/fphar.2019.01287/fullcucurbitacin Cnatural productanti-cancergrowth arrestapoptosisAkt pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dinglan Wu Zhu Wang Muqi Lin Yi Shang Fei Wang JiaYi Zhou Fei Wang Xiantong Zhang Xiaomin Luo Weiren Huang |
spellingShingle |
Dinglan Wu Zhu Wang Muqi Lin Yi Shang Fei Wang JiaYi Zhou Fei Wang Xiantong Zhang Xiaomin Luo Weiren Huang In Vitro and In Vivo Antitumor Activity of Cucurbitacin C, a Novel Natural Product From Cucumber Frontiers in Pharmacology cucurbitacin C natural product anti-cancer growth arrest apoptosis Akt pathway |
author_facet |
Dinglan Wu Zhu Wang Muqi Lin Yi Shang Fei Wang JiaYi Zhou Fei Wang Xiantong Zhang Xiaomin Luo Weiren Huang |
author_sort |
Dinglan Wu |
title |
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_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_sort |
in vitro and in vivo antitumor activity of cucurbitacin c, a novel natural product from cucumber |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2019-11-01 |
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. |
topic |
cucurbitacin C natural product anti-cancer growth arrest apoptosis Akt pathway |
url |
https://www.frontiersin.org/article/10.3389/fphar.2019.01287/full |
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