Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Pang, Dejiang, Li, Chao, Yang, Chengcheng, Zou, Yuanfeng, Feng, Bin, Li, Lixia, Liu, Wentao, Geng, Yi, Luo, Qihui, Chen, Zhengli, Huang, Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
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
_version_ 1783473444854169600
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
work_keys_str_mv AT pangdejiang polyphyllinviipromotesapoptosisandautophagiccelldeathviarosinhibitedaktactivityandsensitizesgliomacellstotemozolomide
AT lichao polyphyllinviipromotesapoptosisandautophagiccelldeathviarosinhibitedaktactivityandsensitizesgliomacellstotemozolomide
AT yangchengcheng polyphyllinviipromotesapoptosisandautophagiccelldeathviarosinhibitedaktactivityandsensitizesgliomacellstotemozolomide
AT zouyuanfeng polyphyllinviipromotesapoptosisandautophagiccelldeathviarosinhibitedaktactivityandsensitizesgliomacellstotemozolomide
AT fengbin polyphyllinviipromotesapoptosisandautophagiccelldeathviarosinhibitedaktactivityandsensitizesgliomacellstotemozolomide
AT lilixia polyphyllinviipromotesapoptosisandautophagiccelldeathviarosinhibitedaktactivityandsensitizesgliomacellstotemozolomide
AT liuwentao polyphyllinviipromotesapoptosisandautophagiccelldeathviarosinhibitedaktactivityandsensitizesgliomacellstotemozolomide
AT gengyi polyphyllinviipromotesapoptosisandautophagiccelldeathviarosinhibitedaktactivityandsensitizesgliomacellstotemozolomide
AT luoqihui polyphyllinviipromotesapoptosisandautophagiccelldeathviarosinhibitedaktactivityandsensitizesgliomacellstotemozolomide
AT chenzhengli polyphyllinviipromotesapoptosisandautophagiccelldeathviarosinhibitedaktactivityandsensitizesgliomacellstotemozolomide
AT huangchao polyphyllinviipromotesapoptosisandautophagiccelldeathviarosinhibitedaktactivityandsensitizesgliomacellstotemozolomide