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Purvalanol A enhances cell killing by inhibiting up-regulation of CDC2 kinase activity in tumor cells irradiated with high doses of X rays.

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タイトル: Purvalanol A enhances cell killing by inhibiting up-regulation of CDC2 kinase activity in tumor cells irradiated with high doses of X rays.
著者: Iizuka, Daisuke 著作を一覧する
Inanami, Osamu 著作を一覧する
Kashiwakura, Ikuo 著作を一覧する
Kuwabara, Mikinori 著作を一覧する
発行日: 2007年 5月
出版者: Radiation Research Society
誌名: Radiation Research
巻: 167
号: 5
開始ページ: 563
終了ページ: 571
出版社 DOI: 10.1667/RR0622.1
抄録: To clarify the relationship between CDC2 kinase activity and radiation-induced apoptosis, we examined whether the cyclin-dependent kinase (CDK) inhibitor purvalanol A enhanced radiation-induced apoptosis in gastric tumor cells. MKN45 cells exposed to 20 Gy of X rays increased the CDC2 kinase activity and the expression of regulatory proteins (phospho-CDC2 and cyclin B1) of the G2/M phase, followed by activation of the G2/M checkpoint, whereas the treatment of X-irradiated MKN45 cells with 20 μM purvalanol A suppressed the increase in the CDC2 kinase activity and expression of the G2/M-phase regulatory proteins and reduced the fraction of the cells in the G2/M phase in the cell cycle. Furthermore, this treatment resulted in not only a significant increase in radiation-induced apoptosis but also the loss of clonogenicity in both MKN45 (p53-wild) and MKN28 (p53-mutated) cells. The expression of anti-apoptosis proteins, inhibitor of apoptosis protein (IAP) family members (survivin and XIAP) and BCL2 family members (Bcl-XL and Bcl-2), in purvalanol A-treated cells with and without X rays was significantly lower than for cells exposed to X rays alone. These results suggest that the inhibition of radiation-induced CDC2 kinase activity by purvalanol A induces apoptosis through the enhancement of active fragments of caspase 3.
資料タイプ: article
URI: http://hdl.handle.net/2115/27975
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 稲波 修

 

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