Costunolide induces mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells

BACKGROUND: Costunolide, a sesquiterpene lactone extracted from Radix Aucklandiae, has the activity against multiple cancers. However, the effect of costunolide on gastric cancer (GC) have remained to be ambiguous. In this study, we investigated the underlying mechanisms of apoptosis induced by cost...

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Autores principales: Yan, Zhanpeng, Xu, Tingting, An, Zhentao, Hu, Ying, Chen, Wanzhen, Ma, Jinxia, Shao, Changle, Zhu, Fangshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595696/
https://www.ncbi.nlm.nih.gov/pubmed/31242894
http://dx.doi.org/10.1186/s12906-019-2569-6
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author Yan, Zhanpeng
Xu, Tingting
An, Zhentao
Hu, Ying
Chen, Wanzhen
Ma, Jinxia
Shao, Changle
Zhu, Fangshi
author_facet Yan, Zhanpeng
Xu, Tingting
An, Zhentao
Hu, Ying
Chen, Wanzhen
Ma, Jinxia
Shao, Changle
Zhu, Fangshi
author_sort Yan, Zhanpeng
collection PubMed
description BACKGROUND: Costunolide, a sesquiterpene lactone extracted from Radix Aucklandiae, has the activity against multiple cancers. However, the effect of costunolide on gastric cancer (GC) have remained to be ambiguous. In this study, we investigated the underlying mechanisms of apoptosis induced by costunolide in human gastric adenocarcinoma BGC-823 cells in vitro and in vivo. METHODS: The viability of BGC-823 cells was detected by MTT assay. The apoptosis and mitochondrial membrane potential (ΔΨm) of BGC-823 cells induced by costunolide were analyzed by flow cytometry. The inhibiton of costunolide on human gastric adenocarcinoma was estimated in xenografts in nude mice. Apoptosis related proteins and genes were detected by Western blot and Q-PCR. RESULTS: Costunolide inhibited the viability of BGC-823 cells in a time and concentration dependent manner. Costunolide induced the apoptosis and lowered the ΔΨm of BGC-823 cells significantly. Costunolide increased the expression of Bax, cleaved caspase 9, cleaved caspase 7, cleaved caspase 3 and cleaved poly ADP ribose polymerase (PARP) proteins and decreased the expression of Bcl-2, pro-caspase 9, pro-caspase 7, pro-caspase 3 and PARP proteins. Costunolide upregulated the expression of puma, Bak1 and Bax mRNA and downregulated the expression of Bcl-2 mRNA. In addition, we demonstrated that costunolide inhibited the growth and induced apoptosis of BGC-823 cells xenografted in athymic nude mice. Costunolide increased the expression of cleaved caspase 9, cleaved caspase 3 and Bax proteins and decreased the expression of Bcl-2 protein in xenografted tumor. Costunolide upregulated the expression of puma and Bax mRNA and decreased the expression of Bcl-2 mRNA in xenografted tumor. CONCLUSIONS: Collectively, our results suggested that costunolide induced mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells and could be the candidate drug against GC in clinical practice.
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spelling pubmed-65956962019-08-07 Costunolide induces mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells Yan, Zhanpeng Xu, Tingting An, Zhentao Hu, Ying Chen, Wanzhen Ma, Jinxia Shao, Changle Zhu, Fangshi BMC Complement Altern Med Research Article BACKGROUND: Costunolide, a sesquiterpene lactone extracted from Radix Aucklandiae, has the activity against multiple cancers. However, the effect of costunolide on gastric cancer (GC) have remained to be ambiguous. In this study, we investigated the underlying mechanisms of apoptosis induced by costunolide in human gastric adenocarcinoma BGC-823 cells in vitro and in vivo. METHODS: The viability of BGC-823 cells was detected by MTT assay. The apoptosis and mitochondrial membrane potential (ΔΨm) of BGC-823 cells induced by costunolide were analyzed by flow cytometry. The inhibiton of costunolide on human gastric adenocarcinoma was estimated in xenografts in nude mice. Apoptosis related proteins and genes were detected by Western blot and Q-PCR. RESULTS: Costunolide inhibited the viability of BGC-823 cells in a time and concentration dependent manner. Costunolide induced the apoptosis and lowered the ΔΨm of BGC-823 cells significantly. Costunolide increased the expression of Bax, cleaved caspase 9, cleaved caspase 7, cleaved caspase 3 and cleaved poly ADP ribose polymerase (PARP) proteins and decreased the expression of Bcl-2, pro-caspase 9, pro-caspase 7, pro-caspase 3 and PARP proteins. Costunolide upregulated the expression of puma, Bak1 and Bax mRNA and downregulated the expression of Bcl-2 mRNA. In addition, we demonstrated that costunolide inhibited the growth and induced apoptosis of BGC-823 cells xenografted in athymic nude mice. Costunolide increased the expression of cleaved caspase 9, cleaved caspase 3 and Bax proteins and decreased the expression of Bcl-2 protein in xenografted tumor. Costunolide upregulated the expression of puma and Bax mRNA and decreased the expression of Bcl-2 mRNA in xenografted tumor. CONCLUSIONS: Collectively, our results suggested that costunolide induced mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells and could be the candidate drug against GC in clinical practice. BioMed Central 2019-06-26 /pmc/articles/PMC6595696/ /pubmed/31242894 http://dx.doi.org/10.1186/s12906-019-2569-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Yan, Zhanpeng
Xu, Tingting
An, Zhentao
Hu, Ying
Chen, Wanzhen
Ma, Jinxia
Shao, Changle
Zhu, Fangshi
Costunolide induces mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells
title Costunolide induces mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells
title_full Costunolide induces mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells
title_fullStr Costunolide induces mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells
title_full_unstemmed Costunolide induces mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells
title_short Costunolide induces mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells
title_sort costunolide induces mitochondria-mediated apoptosis in human gastric adenocarcinoma bgc-823 cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595696/
https://www.ncbi.nlm.nih.gov/pubmed/31242894
http://dx.doi.org/10.1186/s12906-019-2569-6
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