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Hokkaido University Collection of Scholarly and Academic Papers >
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Lipophilic triphenylphosphonium derivatives enhance radiation-induced cell killing via inhibition of mitochondrial energy metabolism in tumor cells
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| Title: | Lipophilic triphenylphosphonium derivatives enhance radiation-induced cell killing via inhibition of mitochondrial energy metabolism in tumor cells |
| Authors: | Yasui, Hironobu Browse this author →KAKEN DB | | Yamamoto, Kumiko Browse this author | | Suzuki, Motofumi Browse this author | | Sakai, Yuri Browse this author | | Bo, Tomoki Browse this author | | Nagane, Masaki Browse this author | | Nishimura, Eri Browse this author | | Yamamori, Tohru Browse this author →KAKEN DB | | Yamasaki, Toshihide Browse this author | | Yamada, Ken-ichi Browse this author | | Inanami, Osamu Browse this author →KAKEN DB |
| Keywords: | ATP | | Cancer | | Mitochondria | | Radiation | | Reactive oxygen species | | Triphenylphosphonium |
| Issue Date: | 1-Apr-2017 |
| Publisher: | Elsevier |
| Journal Title: | Cancer Letters |
| Volume: | 390 |
| Start Page: | 160 |
| End Page: | 167 |
| Publisher DOI: | 10.1016/j.canlet.2017.01.006 |
| PMID: | 28093283 |
| Abstract: | It has recently been reported that radiation enhances mitochondrial energy metabolism in various tumor cell lines. To examine how this radiation-induced alteration in mitochondrial function influences tumor cell viability, various lipophilic triphenylphosphonium (TPP+) cation derivatives and related compounds such as 4-hydroxy-2,2,6,6-tetramethyl-1-oxy-piperidin (Tempol) with TPP+ (named “Mito-”) were designed to inhibit the mitochondrial electron transport chain. Mito-(CH2)10-Tempol (M10T) and its derivatives, Mito-(CH2)5-Tempol (M5T), Mito-(CH2)10-Tempol-Methyl (M10T-Me), Mito-C10H21 (M10), and C10H21-Tempol (10T), were prepared. In HeLa human cervical adenocarcinoma cells and A549 human lung carcinoma cells, the fractional uptake of the compound into mitochondria was highest among the TTP+ analogs conjugated with Tempol (M10T, M5T, and 10T). M10T, M10T-Me, and M10 exhibited strong cytotoxicity and enhanced X-irradiation-induced reproductive cell death, while 10T and M5T did not. Furthermore, M10T, M10T-Me, and M10 decreased basal mitochondrial membrane potential and intracellular ATP. M10T treatment inhibited X-ray-induced increases in ATP production. These results indicate that the TPP cation and a long hydrocarbon linker are essential for radiosensitization of tumor cells. The reduction in intracellular ATP by lipophilic TPP+ is partly responsible for the observed radiosensitization. (c) 2017 Elsevier Ireland Ltd. All rights reserved. |
| Rights: | © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/68704 |
| 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)
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Submitter: 稲波 修
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