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Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways

Piperlongumine (PL) is recently found to kill cancer cells selectively and effectively via targeting reactive oxygen species (ROS) responses. To further explore the therapeutic effects of PL in cancers, we investigated the role and mechanisms of PL in cancer cell migration. PL effectively inhibited...

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Autores principales: Liu, Qian Rong, Liu, Ju Mei, Chen, Yong, Xie, Xiao Qiang, Xiong, Xin Xin, Qiu, Xin Yao, Pan, Feng, Liu, Di, Yu, Shang Bin, Chen, Xiao Qian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055624/
https://www.ncbi.nlm.nih.gov/pubmed/24967005
http://dx.doi.org/10.1155/2014/653732
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author Liu, Qian Rong
Liu, Ju Mei
Chen, Yong
Xie, Xiao Qiang
Xiong, Xin Xin
Qiu, Xin Yao
Pan, Feng
Liu, Di
Yu, Shang Bin
Chen, Xiao Qian
author_facet Liu, Qian Rong
Liu, Ju Mei
Chen, Yong
Xie, Xiao Qiang
Xiong, Xin Xin
Qiu, Xin Yao
Pan, Feng
Liu, Di
Yu, Shang Bin
Chen, Xiao Qian
author_sort Liu, Qian Rong
collection PubMed
description Piperlongumine (PL) is recently found to kill cancer cells selectively and effectively via targeting reactive oxygen species (ROS) responses. To further explore the therapeutic effects of PL in cancers, we investigated the role and mechanisms of PL in cancer cell migration. PL effectively inhibited the migration of human glioma (LN229 or U87 MG) cells but not normal astrocytes in the scratch-wound culture model. PL did not alter EdU(+)-cells and cdc2, cdc25c, or cyclin D1 expression in our model. PL increased ROS (measured by DCFH-DA), reduced glutathione, activated p38 and JNK, increased IκBα, and suppressed NFκB in LN229 cells after scratching. All the biological effects of PL in scratched LN229 cells were completely abolished by the antioxidant N-acetyl-L-cysteine (NAC). Pharmacological administration of specific p38 (SB203580) or JNK (SP600125) inhibitors significantly reduced the inhibitory effects of PL on LN229 cell migration and NFκB activity in scratch-wound and/or transwell models. PL prevented the deformation of migrated LN229 cells while NAC, SB203580, or SP600125 reversed PL-induced morphological changes of migrated cells. These results suggest potential therapeutic effects of PL in the treatment and prevention of highly malignant tumors such as glioblastoma multiforme (GBM) in the brain by suppressing tumor invasion and metastasis.
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spelling pubmed-40556242014-06-25 Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways Liu, Qian Rong Liu, Ju Mei Chen, Yong Xie, Xiao Qiang Xiong, Xin Xin Qiu, Xin Yao Pan, Feng Liu, Di Yu, Shang Bin Chen, Xiao Qian Oxid Med Cell Longev Research Article Piperlongumine (PL) is recently found to kill cancer cells selectively and effectively via targeting reactive oxygen species (ROS) responses. To further explore the therapeutic effects of PL in cancers, we investigated the role and mechanisms of PL in cancer cell migration. PL effectively inhibited the migration of human glioma (LN229 or U87 MG) cells but not normal astrocytes in the scratch-wound culture model. PL did not alter EdU(+)-cells and cdc2, cdc25c, or cyclin D1 expression in our model. PL increased ROS (measured by DCFH-DA), reduced glutathione, activated p38 and JNK, increased IκBα, and suppressed NFκB in LN229 cells after scratching. All the biological effects of PL in scratched LN229 cells were completely abolished by the antioxidant N-acetyl-L-cysteine (NAC). Pharmacological administration of specific p38 (SB203580) or JNK (SP600125) inhibitors significantly reduced the inhibitory effects of PL on LN229 cell migration and NFκB activity in scratch-wound and/or transwell models. PL prevented the deformation of migrated LN229 cells while NAC, SB203580, or SP600125 reversed PL-induced morphological changes of migrated cells. These results suggest potential therapeutic effects of PL in the treatment and prevention of highly malignant tumors such as glioblastoma multiforme (GBM) in the brain by suppressing tumor invasion and metastasis. Hindawi Publishing Corporation 2014 2014-05-22 /pmc/articles/PMC4055624/ /pubmed/24967005 http://dx.doi.org/10.1155/2014/653732 Text en Copyright © 2014 Qian Rong Liu et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liu, Qian Rong
Liu, Ju Mei
Chen, Yong
Xie, Xiao Qiang
Xiong, Xin Xin
Qiu, Xin Yao
Pan, Feng
Liu, Di
Yu, Shang Bin
Chen, Xiao Qian
Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways
title Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways
title_full Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways
title_fullStr Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways
title_full_unstemmed Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways
title_short Piperlongumine Inhibits Migration of Glioblastoma Cells via Activation of ROS-Dependent p38 and JNK Signaling Pathways
title_sort piperlongumine inhibits migration of glioblastoma cells via activation of ros-dependent p38 and jnk signaling pathways
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055624/
https://www.ncbi.nlm.nih.gov/pubmed/24967005
http://dx.doi.org/10.1155/2014/653732
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