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Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS-Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide
The high recurrence frequency of gliomas but deficiency of effective treatment and prevalent chemoresistance have elicited interests in exploring and developing new agents. Paris polyphyllins are monomers extracted from rhizome of Paris polyphylla var. yunnanensis. Here, we first reported that polyp...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877958/ https://www.ncbi.nlm.nih.gov/pubmed/31814867 http://dx.doi.org/10.1155/2019/1805635 |
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author | Pang, Dejiang Li, Chao Yang, Chengcheng Zou, Yuanfeng Feng, Bin Li, Lixia Liu, Wentao Geng, Yi Luo, Qihui Chen, Zhengli Huang, Chao |
author_facet | Pang, Dejiang Li, Chao Yang, Chengcheng Zou, Yuanfeng Feng, Bin Li, Lixia Liu, Wentao Geng, Yi Luo, Qihui Chen, Zhengli Huang, Chao |
author_sort | Pang, Dejiang |
collection | PubMed |
description | The high recurrence frequency of gliomas but deficiency of effective treatment and prevalent chemoresistance have elicited interests in exploring and developing new agents. Paris polyphyllins are monomers extracted from rhizome of Paris polyphylla var. yunnanensis. Here, we first reported that polyphyllin VII (PP7) exhibited cytotoxic effect on glioma cells. PP7 significantly suppressed the viability and induced cell death of U87-MG and U251 cells after 24 h, with the IC50 values 4.24 ± 0.87 μM and 2.17 ± 0.14 μM, respectively. Both apoptotic and autophagic processes were involved in the cytotoxic effect of PP7, as PP7 activated the Bcl2/Bax pathway and the inhibition of autophagy partly rescued the toxicity of PP7 in glioma cells. In addition, an inhibition of AKT/mTORC1 activity was found after PP7 administration, and it seemed that the overproduction of reactive oxygen species (ROS) was responsible for this effect. Namely, the removal of ROS by NAC treatment mitigated PP7-induced cell death, autophagy, and its effect on the AKT/mTORC1 signaling. Additionally, a combination assay of PP7 with temozolomide (TMZ), the most used chemotherapy for glioma patients, was performed resulting in synergism, while PP7 reduced TMZ resistance through inhibition of MGMT expression. Thus, our study reports PP7 as a potential agent for glioma treatment and reveals its underlying mechanisms of action. |
format | Online Article Text |
id | pubmed-6877958 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-68779582019-12-08 Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS-Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide Pang, Dejiang Li, Chao Yang, Chengcheng Zou, Yuanfeng Feng, Bin Li, Lixia Liu, Wentao Geng, Yi Luo, Qihui Chen, Zhengli Huang, Chao Oxid Med Cell Longev Research Article The high recurrence frequency of gliomas but deficiency of effective treatment and prevalent chemoresistance have elicited interests in exploring and developing new agents. Paris polyphyllins are monomers extracted from rhizome of Paris polyphylla var. yunnanensis. Here, we first reported that polyphyllin VII (PP7) exhibited cytotoxic effect on glioma cells. PP7 significantly suppressed the viability and induced cell death of U87-MG and U251 cells after 24 h, with the IC50 values 4.24 ± 0.87 μM and 2.17 ± 0.14 μM, respectively. Both apoptotic and autophagic processes were involved in the cytotoxic effect of PP7, as PP7 activated the Bcl2/Bax pathway and the inhibition of autophagy partly rescued the toxicity of PP7 in glioma cells. In addition, an inhibition of AKT/mTORC1 activity was found after PP7 administration, and it seemed that the overproduction of reactive oxygen species (ROS) was responsible for this effect. Namely, the removal of ROS by NAC treatment mitigated PP7-induced cell death, autophagy, and its effect on the AKT/mTORC1 signaling. Additionally, a combination assay of PP7 with temozolomide (TMZ), the most used chemotherapy for glioma patients, was performed resulting in synergism, while PP7 reduced TMZ resistance through inhibition of MGMT expression. Thus, our study reports PP7 as a potential agent for glioma treatment and reveals its underlying mechanisms of action. Hindawi 2019-11-14 /pmc/articles/PMC6877958/ /pubmed/31814867 http://dx.doi.org/10.1155/2019/1805635 Text en Copyright © 2019 Dejiang Pang et al. http://creativecommons.org/licenses/by/4.0/ 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 Pang, Dejiang Li, Chao Yang, Chengcheng Zou, Yuanfeng Feng, Bin Li, Lixia Liu, Wentao Geng, Yi Luo, Qihui Chen, Zhengli Huang, Chao Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS-Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide |
title | Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS-Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide |
title_full | Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS-Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide |
title_fullStr | Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS-Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide |
title_full_unstemmed | Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS-Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide |
title_short | Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS-Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide |
title_sort | polyphyllin vii promotes apoptosis and autophagic cell death via ros-inhibited akt activity, and sensitizes glioma cells to temozolomide |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877958/ https://www.ncbi.nlm.nih.gov/pubmed/31814867 http://dx.doi.org/10.1155/2019/1805635 |
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