Clinically relevant radioresistant cells exhibit resistance to HO by decreasing internal HO and lipid peroxidation

Radiation therapy is one of the choices to treat malignant tumors. In radiation therapy, existence of radiation-resistant cell is a major problem to overcome. We established clinically relevant radioresistant cells that had been obtained by exposing to 2 Gy/day X-rays for more than 30 days. These ce...

Full description

Saved in:
Bibliographic Details
Main Authors: Kazuo Tomita, Yoshikazu Kuwahara, Yuko Takashi, Kento Igarashi, Taisuke Nagasawa, Hideki Nabika, Akihiro Kurimasa, Manabu Fukumoto, Yoshihiro Nishitani, Tomoaki Sato
Format: Article
Language:English
Published: SAGE Publishing 2018-09-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428318799250
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849411201743716352
author Kazuo Tomita
Yoshikazu Kuwahara
Yuko Takashi
Kento Igarashi
Taisuke Nagasawa
Hideki Nabika
Akihiro Kurimasa
Manabu Fukumoto
Yoshihiro Nishitani
Tomoaki Sato
author_facet Kazuo Tomita
Yoshikazu Kuwahara
Yuko Takashi
Kento Igarashi
Taisuke Nagasawa
Hideki Nabika
Akihiro Kurimasa
Manabu Fukumoto
Yoshihiro Nishitani
Tomoaki Sato
author_sort Kazuo Tomita
collection DOAJ
description Radiation therapy is one of the choices to treat malignant tumors. In radiation therapy, existence of radiation-resistant cell is a major problem to overcome. We established clinically relevant radioresistant cells that had been obtained by exposing to 2 Gy/day X-rays for more than 30 days. These cells are resistant to 2 Gy/day X-ray exposure and anticancer agents. However, the underlying resistance mechanism remains unclear. We investigated the resistance of clinically relevant radioresistant cells to hydrogen peroxide (H 2 O 2 ), confirming a degree of resistance. Neither catalase enzyme activity nor aquaporins appeared to be involved in H 2 O 2 resistance. Mitochondrial DNA copy number, adenosine triphosphate (ATP) concentration, and plasma membrane potential were decreased. The timing of H 2 O 2 intake was delayed and lipid peroxidation was decreased. Sensitivity of clinically relevant radioresistant cells to H 2 O 2 was enhanced by 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero-3-phosphocholine administration. These results suggest that the membrane status is a major factor conferring H 2 O 2 resistance in clinically relevant radioresistant cells, and we should further investigate how membrane status could be used to enhance the therapeutic effect on cancer.
format Article
id doaj-art-8c9e911fa93743dfb51b1f6c358d8422
institution Kabale University
issn 1423-0380
language English
publishDate 2018-09-01
publisher SAGE Publishing
record_format Article
series Tumor Biology
spelling doaj-art-8c9e911fa93743dfb51b1f6c358d84222025-08-20T03:34:51ZengSAGE PublishingTumor Biology1423-03802018-09-014010.1177/1010428318799250Clinically relevant radioresistant cells exhibit resistance to HO by decreasing internal HO and lipid peroxidationKazuo Tomita0Yoshikazu Kuwahara1Yuko Takashi2Kento Igarashi3Taisuke Nagasawa4Hideki Nabika5Akihiro Kurimasa6Manabu Fukumoto7Yoshihiro Nishitani8Tomoaki Sato9Department of Applied Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, JapanDepartment of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, JapanDepartment of Restorative Dentistry and Endodontology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, JapanDepartment of Applied Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, JapanDepartment of Applied Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, JapanDepartment of Material and Biological Chemistry, Faculty of Science, Yamagata University, Yamagata, JapanDepartment of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, JapanDepartment of Molecular Pathology, Tokyo Medical University, Tokyo, JapanDepartment of Restorative Dentistry and Endodontology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, JapanDepartment of Applied Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, JapanRadiation therapy is one of the choices to treat malignant tumors. In radiation therapy, existence of radiation-resistant cell is a major problem to overcome. We established clinically relevant radioresistant cells that had been obtained by exposing to 2 Gy/day X-rays for more than 30 days. These cells are resistant to 2 Gy/day X-ray exposure and anticancer agents. However, the underlying resistance mechanism remains unclear. We investigated the resistance of clinically relevant radioresistant cells to hydrogen peroxide (H 2 O 2 ), confirming a degree of resistance. Neither catalase enzyme activity nor aquaporins appeared to be involved in H 2 O 2 resistance. Mitochondrial DNA copy number, adenosine triphosphate (ATP) concentration, and plasma membrane potential were decreased. The timing of H 2 O 2 intake was delayed and lipid peroxidation was decreased. Sensitivity of clinically relevant radioresistant cells to H 2 O 2 was enhanced by 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero-3-phosphocholine administration. These results suggest that the membrane status is a major factor conferring H 2 O 2 resistance in clinically relevant radioresistant cells, and we should further investigate how membrane status could be used to enhance the therapeutic effect on cancer.https://doi.org/10.1177/1010428318799250
spellingShingle Kazuo Tomita
Yoshikazu Kuwahara
Yuko Takashi
Kento Igarashi
Taisuke Nagasawa
Hideki Nabika
Akihiro Kurimasa
Manabu Fukumoto
Yoshihiro Nishitani
Tomoaki Sato
Clinically relevant radioresistant cells exhibit resistance to HO by decreasing internal HO and lipid peroxidation
Tumor Biology
title Clinically relevant radioresistant cells exhibit resistance to HO by decreasing internal HO and lipid peroxidation
title_full Clinically relevant radioresistant cells exhibit resistance to HO by decreasing internal HO and lipid peroxidation
title_fullStr Clinically relevant radioresistant cells exhibit resistance to HO by decreasing internal HO and lipid peroxidation
title_full_unstemmed Clinically relevant radioresistant cells exhibit resistance to HO by decreasing internal HO and lipid peroxidation
title_short Clinically relevant radioresistant cells exhibit resistance to HO by decreasing internal HO and lipid peroxidation
title_sort clinically relevant radioresistant cells exhibit resistance to ho by decreasing internal ho and lipid peroxidation
url https://doi.org/10.1177/1010428318799250
work_keys_str_mv AT kazuotomita clinicallyrelevantradioresistantcellsexhibitresistancetohobydecreasinginternalhoandlipidperoxidation
AT yoshikazukuwahara clinicallyrelevantradioresistantcellsexhibitresistancetohobydecreasinginternalhoandlipidperoxidation
AT yukotakashi clinicallyrelevantradioresistantcellsexhibitresistancetohobydecreasinginternalhoandlipidperoxidation
AT kentoigarashi clinicallyrelevantradioresistantcellsexhibitresistancetohobydecreasinginternalhoandlipidperoxidation
AT taisukenagasawa clinicallyrelevantradioresistantcellsexhibitresistancetohobydecreasinginternalhoandlipidperoxidation
AT hidekinabika clinicallyrelevantradioresistantcellsexhibitresistancetohobydecreasinginternalhoandlipidperoxidation
AT akihirokurimasa clinicallyrelevantradioresistantcellsexhibitresistancetohobydecreasinginternalhoandlipidperoxidation
AT manabufukumoto clinicallyrelevantradioresistantcellsexhibitresistancetohobydecreasinginternalhoandlipidperoxidation
AT yoshihironishitani clinicallyrelevantradioresistantcellsexhibitresistancetohobydecreasinginternalhoandlipidperoxidation
AT tomoakisato clinicallyrelevantradioresistantcellsexhibitresistancetohobydecreasinginternalhoandlipidperoxidation