Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy

Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy

Radiotherapy is a well-established treatment for cancer. However, the existence of radioresistant cells is one of the major obstacles in radiotherapy. In order to understand the mechanism of cellular radioresistance and develop more effective radiotherapy, we have established clinically relevant rad...

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Main Authors: Kuwahara, Y, Oikawa, T, Ochiai, Y, Roudkenar, M H, Fukumoto, M, Shimura, T, Ohtake, Y, Ohkubo, Y, Mori, S, Uchiyama, Y
Format: Online
Language:English
Published: Nature Publishing Group 2011
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168998/
id pubmed-3168998
recordtype oai_dc
spelling pubmed-31689982011-09-20 Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy Kuwahara, Y Oikawa, T Ochiai, Y Roudkenar, M H Fukumoto, M Shimura, T Ohtake, Y Ohkubo, Y Mori, S Uchiyama, Y Fukumoto, M Original Article Radiotherapy is a well-established treatment for cancer. However, the existence of radioresistant cells is one of the major obstacles in radiotherapy. In order to understand the mechanism of cellular radioresistance and develop more effective radiotherapy, we have established clinically relevant radioresistant (CRR) cell lines, which continue to proliferate under daily exposure to 2 Gray (Gy) of X-rays for >30 days. X-ray irradiation significantly induced autophagic cells in parental cells, which was exiguous in CRR cells, suggesting that autophagic cell death is involved in cellular radiosensitivity. An autophagy inducer, rapamycin sensitized CRR cells to the level of parental cells and suppressed cell growth. An autophagy inhibitor, 3-methyladenine induced radioresistance of parental cells. Furthermore, inhibition of autophagy by knockdown of Beclin-1 made parental cells radioresistant to acute radiation. These suggest that the suppression of autophagic cell death but not apoptosis is mainly involved in cellular radioresistance. Therefore, the enhancement of autophagy may have a considerable impact on the treatment of radioresistant tumor. Nature Publishing Group 2011-06 2011-06-30 /pmc/articles/PMC3168998/ /pubmed/21716292 http://dx.doi.org/10.1038/cddis.2011.56 Text en Copyright © 2011 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Kuwahara, Y
Oikawa, T
Ochiai, Y
Roudkenar, M H
Fukumoto, M
Shimura, T
Ohtake, Y
Ohkubo, Y
Mori, S
Uchiyama, Y
Fukumoto, M
spellingShingle Kuwahara, Y
Oikawa, T
Ochiai, Y
Roudkenar, M H
Fukumoto, M
Shimura, T
Ohtake, Y
Ohkubo, Y
Mori, S
Uchiyama, Y
Fukumoto, M
Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy
author_facet Kuwahara, Y
Oikawa, T
Ochiai, Y
Roudkenar, M H
Fukumoto, M
Shimura, T
Ohtake, Y
Ohkubo, Y
Mori, S
Uchiyama, Y
Fukumoto, M
author_sort Kuwahara, Y
title Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy
title_short Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy
title_full Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy
title_fullStr Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy
title_full_unstemmed Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy
title_sort enhancement of autophagy is a potential modality for tumors refractory to radiotherapy
description Radiotherapy is a well-established treatment for cancer. However, the existence of radioresistant cells is one of the major obstacles in radiotherapy. In order to understand the mechanism of cellular radioresistance and develop more effective radiotherapy, we have established clinically relevant radioresistant (CRR) cell lines, which continue to proliferate under daily exposure to 2 Gray (Gy) of X-rays for >30 days. X-ray irradiation significantly induced autophagic cells in parental cells, which was exiguous in CRR cells, suggesting that autophagic cell death is involved in cellular radiosensitivity. An autophagy inducer, rapamycin sensitized CRR cells to the level of parental cells and suppressed cell growth. An autophagy inhibitor, 3-methyladenine induced radioresistance of parental cells. Furthermore, inhibition of autophagy by knockdown of Beclin-1 made parental cells radioresistant to acute radiation. These suggest that the suppression of autophagic cell death but not apoptosis is mainly involved in cellular radioresistance. Therefore, the enhancement of autophagy may have a considerable impact on the treatment of radioresistant tumor.
publisher Nature Publishing Group
publishDate 2011
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168998/
_version_ 1611474377897934848

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