Cargando…

Inhibition of autophagy using 3-methyladenine increases cisplatin-induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells

Cisplatin is one of the most widely used chemotherapeutic drugs; however, the side effects and drug resistance limit its usage. Previous findings have demonstrated that cisplatin kills tumor cells through endoplasmic reticulum (ER) stress, which provides a novel method to minimize cisplatin toxicity...

Descripción completa

Detalles Bibliográficos
Autores principales: ZHANG, RUIJIAN, WANG, RUIJUN, CHEN, QIANXUE, CHANG, HONG
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464427/
https://www.ncbi.nlm.nih.gov/pubmed/25846607
http://dx.doi.org/10.3892/mmr.2015.3588
_version_ 1782375967356878848
author ZHANG, RUIJIAN
WANG, RUIJUN
CHEN, QIANXUE
CHANG, HONG
author_facet ZHANG, RUIJIAN
WANG, RUIJUN
CHEN, QIANXUE
CHANG, HONG
author_sort ZHANG, RUIJIAN
collection PubMed
description Cisplatin is one of the most widely used chemotherapeutic drugs; however, the side effects and drug resistance limit its usage. Previous findings have demonstrated that cisplatin kills tumor cells through endoplasmic reticulum (ER) stress, which provides a novel method to minimize cisplatin toxicity and circumvent cisplatin resistance. ER stress induces cell autophagy, cell apoptosis and the complicated regulatory network between them. The role of autophagy in cisplatin chemotherapy remains to be elucidated. 3-Methyladenine (3-MA) is normally used as an inhibitor of autophagy. The present study reveals a significant role of the inhibition of autophagy by treatment with 3-MA and cisplatin in combination in U251 human glioma cells. It was demonstrated that cisplatin induced the ER stress associated with apoptosis and autophagy in U251 cells. Inhibition of autophagy by 3-MA increased the expression levels of protein disulfide isomerase, ubiquitinated proteins, glucose regulated protein 78 and CCAAT-enhancer-binding protein homologous protein, and induced the activation of caspase-4 and caspase-3. Treatment with 3-MA combined with cisplatin increased cisplatin-induced apoptosis by increasing ER stress. Therefore, the inhibition of autophagy has the potential to improve cisplatin chemotherapy.
format Online
Article
Text
id pubmed-4464427
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-44644272015-06-26 Inhibition of autophagy using 3-methyladenine increases cisplatin-induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells ZHANG, RUIJIAN WANG, RUIJUN CHEN, QIANXUE CHANG, HONG Mol Med Rep Articles Cisplatin is one of the most widely used chemotherapeutic drugs; however, the side effects and drug resistance limit its usage. Previous findings have demonstrated that cisplatin kills tumor cells through endoplasmic reticulum (ER) stress, which provides a novel method to minimize cisplatin toxicity and circumvent cisplatin resistance. ER stress induces cell autophagy, cell apoptosis and the complicated regulatory network between them. The role of autophagy in cisplatin chemotherapy remains to be elucidated. 3-Methyladenine (3-MA) is normally used as an inhibitor of autophagy. The present study reveals a significant role of the inhibition of autophagy by treatment with 3-MA and cisplatin in combination in U251 human glioma cells. It was demonstrated that cisplatin induced the ER stress associated with apoptosis and autophagy in U251 cells. Inhibition of autophagy by 3-MA increased the expression levels of protein disulfide isomerase, ubiquitinated proteins, glucose regulated protein 78 and CCAAT-enhancer-binding protein homologous protein, and induced the activation of caspase-4 and caspase-3. Treatment with 3-MA combined with cisplatin increased cisplatin-induced apoptosis by increasing ER stress. Therefore, the inhibition of autophagy has the potential to improve cisplatin chemotherapy. D.A. Spandidos 2015-08 2015-04-01 /pmc/articles/PMC4464427/ /pubmed/25846607 http://dx.doi.org/10.3892/mmr.2015.3588 Text en Copyright © 2015, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
ZHANG, RUIJIAN
WANG, RUIJUN
CHEN, QIANXUE
CHANG, HONG
Inhibition of autophagy using 3-methyladenine increases cisplatin-induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells
title Inhibition of autophagy using 3-methyladenine increases cisplatin-induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells
title_full Inhibition of autophagy using 3-methyladenine increases cisplatin-induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells
title_fullStr Inhibition of autophagy using 3-methyladenine increases cisplatin-induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells
title_full_unstemmed Inhibition of autophagy using 3-methyladenine increases cisplatin-induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells
title_short Inhibition of autophagy using 3-methyladenine increases cisplatin-induced apoptosis by increasing endoplasmic reticulum stress in U251 human glioma cells
title_sort inhibition of autophagy using 3-methyladenine increases cisplatin-induced apoptosis by increasing endoplasmic reticulum stress in u251 human glioma cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464427/
https://www.ncbi.nlm.nih.gov/pubmed/25846607
http://dx.doi.org/10.3892/mmr.2015.3588
work_keys_str_mv AT zhangruijian inhibitionofautophagyusing3methyladenineincreasescisplatininducedapoptosisbyincreasingendoplasmicreticulumstressinu251humangliomacells
AT wangruijun inhibitionofautophagyusing3methyladenineincreasescisplatininducedapoptosisbyincreasingendoplasmicreticulumstressinu251humangliomacells
AT chenqianxue inhibitionofautophagyusing3methyladenineincreasescisplatininducedapoptosisbyincreasingendoplasmicreticulumstressinu251humangliomacells
AT changhong inhibitionofautophagyusing3methyladenineincreasescisplatininducedapoptosisbyincreasingendoplasmicreticulumstressinu251humangliomacells