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Zeylenone Induces Mitochondrial Apoptosis and Inhibits Migration and Invasion in Gastric Cancer

The mortality of gastric cancer (GC) is increasing due to its high rates of recurrence and metastasis. Zeylenone (Zey), a type of naturally occurring cyclohexene oxide, was demonstrated to be effective in cancer patients. The aim of this study is to explore the anti-cancer effect of Zey against gast...

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Autores principales: Yang, Shuxian, Liao, Yonghong, Li, Liyong, Xu, Xudong, Cao, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225419/
https://www.ncbi.nlm.nih.gov/pubmed/30150551
http://dx.doi.org/10.3390/molecules23092149
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author Yang, Shuxian
Liao, Yonghong
Li, Liyong
Xu, Xudong
Cao, Li
author_facet Yang, Shuxian
Liao, Yonghong
Li, Liyong
Xu, Xudong
Cao, Li
author_sort Yang, Shuxian
collection PubMed
description The mortality of gastric cancer (GC) is increasing due to its high rates of recurrence and metastasis. Zeylenone (Zey), a type of naturally occurring cyclohexene oxide, was demonstrated to be effective in cancer patients. The aim of this study is to explore the anti-cancer effect of Zey against gastric cancer both in vitro and in vivo, as well as the underlying mechanisms. We found that Zey inhibited gastric tumor growth, as demonstrated by in vitro gastric cancer cell lines and in a human gastric cancer xenograft mouse model. Furthermore, Zey induced substantial apoptosis through a mitochondrial apoptotic pathway, involving mitochondrial transmembrane potential loss, caspase-3 activation, anti-apoptotic protein downregulation, and pro-apoptotic protein upregulation. Notably, we revealed for the first time that Zey suppressed invasion and migration by wound healing and transwell chamber assays. Through Western blotting, we further explored the potential mechanism of Zey’s anti-cancer activity. We found that Zey downregulated the expression of matrix metalloproteinase 2/9 (MMP 2/9) and inhibited the phosphorylation of AKT and ERK. In short, Zey, which induced mitochondrial apoptosis and inhibited proliferation, migration, and invasion, may be developed as a novel drug for the treatment of gastric cancer.
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spelling pubmed-62254192018-11-13 Zeylenone Induces Mitochondrial Apoptosis and Inhibits Migration and Invasion in Gastric Cancer Yang, Shuxian Liao, Yonghong Li, Liyong Xu, Xudong Cao, Li Molecules Article The mortality of gastric cancer (GC) is increasing due to its high rates of recurrence and metastasis. Zeylenone (Zey), a type of naturally occurring cyclohexene oxide, was demonstrated to be effective in cancer patients. The aim of this study is to explore the anti-cancer effect of Zey against gastric cancer both in vitro and in vivo, as well as the underlying mechanisms. We found that Zey inhibited gastric tumor growth, as demonstrated by in vitro gastric cancer cell lines and in a human gastric cancer xenograft mouse model. Furthermore, Zey induced substantial apoptosis through a mitochondrial apoptotic pathway, involving mitochondrial transmembrane potential loss, caspase-3 activation, anti-apoptotic protein downregulation, and pro-apoptotic protein upregulation. Notably, we revealed for the first time that Zey suppressed invasion and migration by wound healing and transwell chamber assays. Through Western blotting, we further explored the potential mechanism of Zey’s anti-cancer activity. We found that Zey downregulated the expression of matrix metalloproteinase 2/9 (MMP 2/9) and inhibited the phosphorylation of AKT and ERK. In short, Zey, which induced mitochondrial apoptosis and inhibited proliferation, migration, and invasion, may be developed as a novel drug for the treatment of gastric cancer. MDPI 2018-08-27 /pmc/articles/PMC6225419/ /pubmed/30150551 http://dx.doi.org/10.3390/molecules23092149 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yang, Shuxian
Liao, Yonghong
Li, Liyong
Xu, Xudong
Cao, Li
Zeylenone Induces Mitochondrial Apoptosis and Inhibits Migration and Invasion in Gastric Cancer
title Zeylenone Induces Mitochondrial Apoptosis and Inhibits Migration and Invasion in Gastric Cancer
title_full Zeylenone Induces Mitochondrial Apoptosis and Inhibits Migration and Invasion in Gastric Cancer
title_fullStr Zeylenone Induces Mitochondrial Apoptosis and Inhibits Migration and Invasion in Gastric Cancer
title_full_unstemmed Zeylenone Induces Mitochondrial Apoptosis and Inhibits Migration and Invasion in Gastric Cancer
title_short Zeylenone Induces Mitochondrial Apoptosis and Inhibits Migration and Invasion in Gastric Cancer
title_sort zeylenone induces mitochondrial apoptosis and inhibits migration and invasion in gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225419/
https://www.ncbi.nlm.nih.gov/pubmed/30150551
http://dx.doi.org/10.3390/molecules23092149
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