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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.

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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)

Submitter: 稲波 修

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