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Evodiamine Induces Apoptosis in SMMC-7721 and HepG2 Cells by Suppressing NOD1 Signal Pathway

Hepatocellular cancer (HCC) is a lethal malignancy with poor prognosis and easy recurrence. There are few agents with minor toxic side effects that can be used for treatment of HCC. Evodiamine (Evo), one of the major bioactive components derived from fructus Evodiae, has long been shown to exert ant...

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Autores principales: Guo, Xing-Xian, Li, Xiao-Peng, Zhou, Peng, Li, Dan-Yang, Lyu, Xiao-Ting, Chen, Yi, Lyu, Yan-Wei, Tian, Kuan, Yuan, De-Zhi, Ran, Jian-Hua, Chen, Di-Long, Jiang, Rong, Li, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274686/
https://www.ncbi.nlm.nih.gov/pubmed/30384473
http://dx.doi.org/10.3390/ijms19113419
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author Guo, Xing-Xian
Li, Xiao-Peng
Zhou, Peng
Li, Dan-Yang
Lyu, Xiao-Ting
Chen, Yi
Lyu, Yan-Wei
Tian, Kuan
Yuan, De-Zhi
Ran, Jian-Hua
Chen, Di-Long
Jiang, Rong
Li, Jing
author_facet Guo, Xing-Xian
Li, Xiao-Peng
Zhou, Peng
Li, Dan-Yang
Lyu, Xiao-Ting
Chen, Yi
Lyu, Yan-Wei
Tian, Kuan
Yuan, De-Zhi
Ran, Jian-Hua
Chen, Di-Long
Jiang, Rong
Li, Jing
author_sort Guo, Xing-Xian
collection PubMed
description Hepatocellular cancer (HCC) is a lethal malignancy with poor prognosis and easy recurrence. There are few agents with minor toxic side effects that can be used for treatment of HCC. Evodiamine (Evo), one of the major bioactive components derived from fructus Evodiae, has long been shown to exert anti-hepatocellular carcinoma activity by suppressing activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK). In addition, in the Nucleotide-Binding Oligomerization Domain 1 (NOD1) pathway, NOD1 could initiate NF-κB-dependent and MAPK-dependent gene transcription. Recent experimental studies reported that the NOD1 pathway was related to controlling development of various tumors. Here we hypothesize that Evo exerts anti-hepatocellular carcinoma activity by inhibiting NOD1 to suppress NF-κB and MAPK activation. Therefore, we proved the anti-hepatocellular carcinoma activity of Evo on HCC cells and detected the effect of Evo on the NOD1 pathway. We found that Evo significantly induced cell cycle arrest at the G2/M phase, upregulated P53 and Bcl-2 associated X proteins (Bax) proteins, and downregulated B-cell lymphoma-2 (Bcl-2), cyclinB1, and cdc2 proteins in HCC cells. In addition, Evo reduced levels of NOD1, p-P65, p-ERK, p-p38, and p-JNK, where the level of IκBα of HCC cells increased. Furthermore, NOD1 agonist γ-D-Glu-mDAP (IE-DAP) treatment weakened the effect of Evo on suppression of NF-κB and MAPK activation and cellular proliferation of HCC. In an in vivo subcutaneous xenograft model, Evo also exhibited excellent tumor inhibitory effects via the NOD1 signal pathway. Our results demonstrate that Evo could induce apoptosis remarkably and the inhibitory effect of Evo on HCC cells may be through suppressing the NOD1 signal pathway in vitro and in vivo.
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spelling pubmed-62746862018-12-15 Evodiamine Induces Apoptosis in SMMC-7721 and HepG2 Cells by Suppressing NOD1 Signal Pathway Guo, Xing-Xian Li, Xiao-Peng Zhou, Peng Li, Dan-Yang Lyu, Xiao-Ting Chen, Yi Lyu, Yan-Wei Tian, Kuan Yuan, De-Zhi Ran, Jian-Hua Chen, Di-Long Jiang, Rong Li, Jing Int J Mol Sci Article Hepatocellular cancer (HCC) is a lethal malignancy with poor prognosis and easy recurrence. There are few agents with minor toxic side effects that can be used for treatment of HCC. Evodiamine (Evo), one of the major bioactive components derived from fructus Evodiae, has long been shown to exert anti-hepatocellular carcinoma activity by suppressing activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK). In addition, in the Nucleotide-Binding Oligomerization Domain 1 (NOD1) pathway, NOD1 could initiate NF-κB-dependent and MAPK-dependent gene transcription. Recent experimental studies reported that the NOD1 pathway was related to controlling development of various tumors. Here we hypothesize that Evo exerts anti-hepatocellular carcinoma activity by inhibiting NOD1 to suppress NF-κB and MAPK activation. Therefore, we proved the anti-hepatocellular carcinoma activity of Evo on HCC cells and detected the effect of Evo on the NOD1 pathway. We found that Evo significantly induced cell cycle arrest at the G2/M phase, upregulated P53 and Bcl-2 associated X proteins (Bax) proteins, and downregulated B-cell lymphoma-2 (Bcl-2), cyclinB1, and cdc2 proteins in HCC cells. In addition, Evo reduced levels of NOD1, p-P65, p-ERK, p-p38, and p-JNK, where the level of IκBα of HCC cells increased. Furthermore, NOD1 agonist γ-D-Glu-mDAP (IE-DAP) treatment weakened the effect of Evo on suppression of NF-κB and MAPK activation and cellular proliferation of HCC. In an in vivo subcutaneous xenograft model, Evo also exhibited excellent tumor inhibitory effects via the NOD1 signal pathway. Our results demonstrate that Evo could induce apoptosis remarkably and the inhibitory effect of Evo on HCC cells may be through suppressing the NOD1 signal pathway in vitro and in vivo. MDPI 2018-10-31 /pmc/articles/PMC6274686/ /pubmed/30384473 http://dx.doi.org/10.3390/ijms19113419 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
Guo, Xing-Xian
Li, Xiao-Peng
Zhou, Peng
Li, Dan-Yang
Lyu, Xiao-Ting
Chen, Yi
Lyu, Yan-Wei
Tian, Kuan
Yuan, De-Zhi
Ran, Jian-Hua
Chen, Di-Long
Jiang, Rong
Li, Jing
Evodiamine Induces Apoptosis in SMMC-7721 and HepG2 Cells by Suppressing NOD1 Signal Pathway
title Evodiamine Induces Apoptosis in SMMC-7721 and HepG2 Cells by Suppressing NOD1 Signal Pathway
title_full Evodiamine Induces Apoptosis in SMMC-7721 and HepG2 Cells by Suppressing NOD1 Signal Pathway
title_fullStr Evodiamine Induces Apoptosis in SMMC-7721 and HepG2 Cells by Suppressing NOD1 Signal Pathway
title_full_unstemmed Evodiamine Induces Apoptosis in SMMC-7721 and HepG2 Cells by Suppressing NOD1 Signal Pathway
title_short Evodiamine Induces Apoptosis in SMMC-7721 and HepG2 Cells by Suppressing NOD1 Signal Pathway
title_sort evodiamine induces apoptosis in smmc-7721 and hepg2 cells by suppressing nod1 signal pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274686/
https://www.ncbi.nlm.nih.gov/pubmed/30384473
http://dx.doi.org/10.3390/ijms19113419
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