HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine >
Peer-reviewed Journal Articles, etc >

Preclinical studies for improving radiosensitivity of non-small cell lung cancer cell lines by combining glutaminase inhibition and senolysis

Files in This Item:

The file(s) associated with this item can be obtained from the following URL: https://doi.org/10.1016/j.tranon.2022.101431


Title: Preclinical studies for improving radiosensitivity of non-small cell lung cancer cell lines by combining glutaminase inhibition and senolysis
Authors: Fujimoto, Masaki Browse this author
Higashiyama, Ritsuko Browse this author
Yasui, Hironobu Browse this author
Yamashita, Koya Browse this author
Inanami, Osamu Browse this author →KAKEN DB
Keywords: Radiation
Glutaminolysis
Senescence
Senolytic drug
Apoptosis
Issue Date: 1-Jul-2022
Publisher: Elsevier
Journal Title: Translational Oncology
Volume: 21
Start Page: 101431
Publisher DOI: 10.1016/j.tranon.2022.101431
Abstract: Glutamine metabolism, known as glutaminolysis, is abnormally activated in many cancer cells with KRAS or BRAF mutations or active c-MYC. Glutaminolysis plays an important role in the proliferation of cancer cells with oncogenic mutations. In this study, we characterized radiation-induced cell death, which was enhanced by glutaminolysis inhibition in non-small cell lung cancer A549 and H460 cell lines with KRAS mutation. A clonogenic survival assay revealed that treatment with a glutaminase inhibitor, CB839, enhanced radiosensitivity. X-irradiation increased glutamate production, mitochondrial oxygen consumption, and ATP production, whereas CB839 treatment suppressed these effects. The data suggest that the enhancement of glutaminolysis-dependent energy metabolism for ATP production is important for survival after X-irradiation. Evaluation of the cell death phenotype revealed that glutaminolysis inhibitory treatment with CB839 or a low-glutamine medium significantly promoted the proliferation of beta-galactosidase-positive and IL-6/IL-8 secretory cells among X-irradiated tumor cells, corresponding to an increase in the senescent cell population. Furthermore, treatment with ABT263, a Bcl-2 family inhibitor, transformed senescent cells into apoptotic cells. The findings suggest that combination treatment with a glutaminolysis inhibitor and a senolytic drug is useful for efficient radiotherapy.
Type: article
URI: http://hdl.handle.net/2115/86590
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Export metadata:

OAI-PMH ( junii2 , jpcoar_1.0 )

MathJax is now OFF:


 

 - Hokkaido University