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 >

A nucleoside anticancer drug, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (TAS106), sensitizes cells to radiation by suppressing BRCA2 expression

Creative Commons License

Files in This Item:
1476-4598-10-92.pdf2.34 MBPDFView/Open
Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/46978

Title: A nucleoside anticancer drug, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (TAS106), sensitizes cells to radiation by suppressing BRCA2 expression
Authors: Meike, Shunsuke Browse this author
Yamamori, Tohru Browse this author →KAKEN DB
Yasui, Hironobu Browse this author →KAKEN DB
Eitaki, Masato Browse this author
Matsuda, Akira Browse this author →KAKEN DB
Morimatsu, Masami Browse this author →KAKEN DB
Fukushima, Masakazu Browse this author
Yamasaki, Yasundo Browse this author
Inanami, Osamu Browse this author →KAKEN DB
Keywords: radiation
DNA repair
homologous recombination
Issue Date: Jul-2011
Publisher: BioMed Central
Journal Title: Molecular Cancer
Volume: 10
Issue: 1
Start Page: 92
Publisher DOI: 10.1186/1476-4598-10-92
Abstract: Background: A novel anticancer drug 1-(3-C-ethynyl-b-D-ribo-pentofuranosyl)cytosine (ECyd, TAS106) has been shown to radiosensitize tumor cells and to improve the therapeutic efficiency of X-irradiation. However, the effect of TAS106 on cellular DNA repair capacity has not been elucidated. Our aim in this study was to examine whether TAS106 modified the repair capacity of DNA double-strand breaks (DSBs) in tumor cells. Methods: Various cultured cell lines treated with TAS106 were irradiated and then survival fraction was examined by the clonogenic survival assays. Repair of sublethal damage (SLD), which indicates DSBs repair capacity, was measured as an increase of surviving cells after split dose irradiation with an interval of incubation. To assess the effect of TAS106 on the DSBs repair activity, the time courses of g-H2AX and 53BP1 foci formation were examined by using immunocytochemistry. The expression of DNA-repair-related proteins was also examined by Western blot analysis and semi-quantitative RT-PCR analysis. Results: In clonogenic survival assays, pretreatment of TAS106 showed radiosensitizing effects in various cell lines. TAS106 inhibited SLD repair and delayed the disappearance of g-H2AX and 53BP1 foci, suggesting that DSB repair occurred in A549 cells. Western blot analysis demonstrated that TAS106 down-regulated the expression of BRCA2 and Rad51, which are known as keys among DNA repair proteins in the homologous recombination (HR) pathway. Although a significant radiosensitizing effect of TAS106 was observed in the parental V79 cells, pretreatment with TAS106 did not induce any radiosensitizing effects in BRCA2-deficient V-C8 cells. Conclusions: Our results indicate that TAS106 induces the down-regulation of BRCA2 and the subsequent abrogation of the HR pathway, leading to a radiosensitizing effect. Therefore, this study suggests that inhibition of the HR pathway may be useful to improve the therapeutic efficiency of radiotherapy for solid tumors.
Rights: http://creativecommons.org/licenses/by-nc-sa/2.1/jp/
Type: article
URI: http://hdl.handle.net/2115/46978
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

Export metadata:

OAI-PMH ( junii2 , jpcoar )


 

Feedback - Hokkaido University