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A novel anticancer ribonucleoside, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine, enhances radiation-induced cell death in tumor cells.
Title: | A novel anticancer ribonucleoside, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine, enhances radiation-induced cell death in tumor cells. |
Authors: | Inanami, Osamu Browse this author →KAKEN DB | Iizuka, Daisuke Browse this author | Iwahara, Akiko Browse this author | Yamamori, Tohru Browse this author →KAKEN DB | Kon, Yasuhiro Browse this author →KAKEN DB | Asanuma, Taketoshi Browse this author | Matsuda, Akira Browse this author →KAKEN DB | Kashiwakura, Ikuo Browse this author | Kitazato, Kenji Browse this author | Kuwabara, Mikinori Browse this author |
Issue Date: | Dec-2004 |
Publisher: | Radiation Research Society |
Journal Title: | Radiation Research |
Volume: | 162 |
Issue: | 6 |
Start Page: | 635 |
End Page: | 645 |
Publisher DOI: | 10.1667/RR3268 |
PMID: | 15548113 |
Abstract: | 1-(3-C-Ethynyl-β-d-ribo-pentofuranosyl)cytosine (ECyd, TAS106) is a newly developed anti-tumor agent that targets RNA synthesis. We report here that a low dose of ECyd induces radiosensitization of caspase-dependent apoptosis and reproductive cell death in cells of the gastric tumor cell lines MKN45 and MKN28 and murine rectum adenocarcinoma Colon26. Flow cytometry demonstrated that TAS106 induced the abrogation of the X-ray-induced G2/M checkpoint. Western blot analysis showed that X rays increased the expression of cyclin B1, phospho-Cdc2 and Wee1, whereas co-treatment with X rays and TAS106 decreased the expression of these cell cycle proteins associated with the G2/M checkpoint. Furthermore, TAS106 was shown to decrease the radiation-induced expression of survivin but not Bcl2 and BclXL regardless of TP53 status and cell type. Overexpression of wild-type survivin in MKN45 cells inhibited the induction of apoptosis induced by co-treatment with X rays and TAS106. These results suggest that TAS106 enhances X-ray-induced cell death through down-regulation of survivin and abrogation of the cell cycle machinery. |
Type: | article |
URI: | http://hdl.handle.net/2115/27978 |
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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