Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling

In the past decades, hepatocellular carcinoma (HCC) has been receiving increased attention due to rising morbidity and mortality in both developing and developed countries. Koumine, one of the significant alkaloidal constituents of <i>Gelsemium elegans</i> Benth., has been regarded as a...

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Main Authors: Zhihang Yuan, Zengenni Liang, Jine Yi, Xiaojun Chen, Rongfang Li, Jing Wu, Zhiliang Sun
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/9/10/559
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author Zhihang Yuan
Zengenni Liang
Jine Yi
Xiaojun Chen
Rongfang Li
Jing Wu
Zhiliang Sun
author_facet Zhihang Yuan
Zengenni Liang
Jine Yi
Xiaojun Chen
Rongfang Li
Jing Wu
Zhiliang Sun
author_sort Zhihang Yuan
collection DOAJ
description In the past decades, hepatocellular carcinoma (HCC) has been receiving increased attention due to rising morbidity and mortality in both developing and developed countries. Koumine, one of the significant alkaloidal constituents of <i>Gelsemium elegans</i> Benth., has been regarded as a promising anti-inflammation, anxiolytic, and analgesic agent, as well as an anti-tumor agent. In the present study, we attempted to provide a novel mechanism by which koumine suppresses HCC cell proliferation. We demonstrated that koumine might suppress the proliferation of HCC cells and promote apoptosis in HCC cells dose-dependently. Under koumine treatment, the mitochondria membrane potential was significantly decreased while reactive oxygen species (ROS) production was increased in HCC cells; in the meantime, the phosphorylation of ERK, p38, p65, and I&#954;B&#945; could all be inhibited by koumine treatment dose-dependently. More importantly, the effects of koumine upon mitochondria membrane potential, ROS production, and the phosphorylation of ERK, p38, p65, and I&#954;B&#945; could be significantly reversed by ROS inhibitor, indicating that koumine affects HCC cell fate and ERK/p38 MAPK and NF-&#954;B signaling activity through producing excess ROS. In conclusion, koumine could inhibit the proliferation of HCC cells and promote apoptosis in HCC cells; NF-&#954;B and ERK/p38 MAPK pathways could contribute to koumine functions in a ROS-dependent manner.
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spelling doaj.art-4c3a0074ea2c4239863186ca67b03f992022-12-22T00:17:00ZengMDPI AGBiomolecules2218-273X2019-10-0191055910.3390/biom9100559biom9100559Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK SignalingZhihang Yuan0Zengenni Liang1Jine Yi2Xiaojun Chen3Rongfang Li4Jing Wu5Zhiliang Sun6Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, ChinaDepartment of Hunan Agricultural Product Processing Institute, Changsha 410128, ChinaDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, ChinaDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, ChinaDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, ChinaDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, ChinaDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, ChinaIn the past decades, hepatocellular carcinoma (HCC) has been receiving increased attention due to rising morbidity and mortality in both developing and developed countries. Koumine, one of the significant alkaloidal constituents of <i>Gelsemium elegans</i> Benth., has been regarded as a promising anti-inflammation, anxiolytic, and analgesic agent, as well as an anti-tumor agent. In the present study, we attempted to provide a novel mechanism by which koumine suppresses HCC cell proliferation. We demonstrated that koumine might suppress the proliferation of HCC cells and promote apoptosis in HCC cells dose-dependently. Under koumine treatment, the mitochondria membrane potential was significantly decreased while reactive oxygen species (ROS) production was increased in HCC cells; in the meantime, the phosphorylation of ERK, p38, p65, and I&#954;B&#945; could all be inhibited by koumine treatment dose-dependently. More importantly, the effects of koumine upon mitochondria membrane potential, ROS production, and the phosphorylation of ERK, p38, p65, and I&#954;B&#945; could be significantly reversed by ROS inhibitor, indicating that koumine affects HCC cell fate and ERK/p38 MAPK and NF-&#954;B signaling activity through producing excess ROS. In conclusion, koumine could inhibit the proliferation of HCC cells and promote apoptosis in HCC cells; NF-&#954;B and ERK/p38 MAPK pathways could contribute to koumine functions in a ROS-dependent manner.https://www.mdpi.com/2218-273X/9/10/559hepatocellular carcinoma (hcc)kouminerosproliferationnf-κb and erk/p38 mapk signaling
spellingShingle Zhihang Yuan
Zengenni Liang
Jine Yi
Xiaojun Chen
Rongfang Li
Jing Wu
Zhiliang Sun
Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling
Biomolecules
hepatocellular carcinoma (hcc)
koumine
ros
proliferation
nf-κb and erk/p38 mapk signaling
title Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling
title_full Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling
title_fullStr Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling
title_full_unstemmed Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling
title_short Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling
title_sort koumine promotes ros production to suppress hepatocellular carcinoma cell proliferation via nf κb and erk p38 mapk signaling
topic hepatocellular carcinoma (hcc)
koumine
ros
proliferation
nf-κb and erk/p38 mapk signaling
url https://www.mdpi.com/2218-273X/9/10/559
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