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

Meike, Shunsuke; Yamamori, Tohru; Yasui, Hironobu; Eitaki, Masato; Matsuda, Akira; Morimatsu, Masami; Fukushima, Masakazu; Yamasaki, Yasundo; Inanami, Osamu

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

Meike, Shunsuke; Yamamori, Tohru; Yasui, Hironobu et al.

Molecular Cancer, 2011, 10(1), 92

Permalink : https://hdl.handle.net/2115/46978

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アクセス権	open access
URI	https://hdl.handle.net/2115/46978
タイトル	A nucleoside anticancer drug, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (TAS106), sensitizes cells to radiation by suppressing BRCA2 expression
著者	Meike, Shunsuke ; Yamamori, Tohru ; Yasui, Hironobu ; Eitaki, Masato ; Matsuda, Akira ; Morimatsu, Masami ; Fukushima, Masakazu ; Yamasaki, Yasundo ; Inanami, Osamu
著者名 Meike, Shunsuke
e-Rad_Researcher 00512675 著者名 Yamamori, Tohru
e-Rad_Researcher 10570228 著者名 Yasui, Hironobu
著者名 Eitaki, Masato
e-Rad_Researcher 90157313 著者名 Matsuda, Akira
e-Rad_Researcher 70241370 著者名 Morimatsu, Masami
著者名 Fukushima, Masakazu
著者名 Yamasaki, Yasundo
e-Rad_Researcher 10193559 著者名 Inanami, Osamu
言語	英語
キーワード	radiation
	DNA repair
	homologous recombination
発行日	2011-07
出版者	BioMed Central
収録物名	Molecular Cancer
巻(号)	10(1)
ページ	92
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution-NonCommercial-ShareAlike 2.1 Japan
PISSN	1476-4598
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1186/1476-4598-10-92