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Enhancement of radiation-induced cell killing by inhibiting G2 checkpoint with purvalanol A.
https://repo.qst.go.jp/records/69044
https://repo.qst.go.jp/records/6904471145121-e1f4-4bee-8ca3-0f4903d85fa4
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2007-07-20 | |||||
| タイトル | ||||||
| タイトル | Enhancement of radiation-induced cell killing by inhibiting G2 checkpoint with purvalanol A. | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Iizuka, Daisuke
× Iizuka, Daisuke× et.al× 飯塚 大輔 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | [Purpose] Ionizing radiation is known to cause cell-cycle arrest at G2 phase in various tumor cells. Recently, treatment with drugs such as UCN-01 and caffeine induces cell killing in X-irradiated tumor cells through the abrogation of G2 checkpoint. In this study, we focus on Cdc2 and investigated the mechanism of enhancement of radiation-induced cell killing by the inhibition of Cdc2 kinase activity with cyclin dependent kinase (cdk) inhibitor purvalanol A. \n[Materials and Methods] Human gastric adenocarcinoma MKN45 (wild p53) and MKN28 (mutated p53) cells were exposed to X rays with or without purvalanol A. For measurements of apoptosis, apoptotic morphological changes of nuclei were assessed by fluorescence microscopy. Cell cycle distribution was observed by flow-cytometry. Observation of Cdc2 kinase activity was performed using Cdc2-associated histone H1 kinase assay. Expression of mRNA was assessed by semi-quantitative RT-PCR. Expression of proteins was assessed by Western blotting with corresponding antibodies. \n[Results and Discussion] Cotreatment of cells with X rays and purvalanol A induced the significant increase in the number of apoptosis in MKN45 and MKN28 cells. When cells were exposed to X rays alone, G2/M arrest occurred. Cotreatment of X rays with purvalanol A rendered the decrease in G2/M fraction and the increase in subG1 fraction. Treatment of cells with X rays increased the expression of proteins relating to the G2 checkpoint and Cdc2 kinase activity and resulted in the G2 arrest, and purvalanol A decreased the expression of the G2-related proteins and the Cdc2 kinase activity. On the expression of anti-apoptotic proteins, purvalanol A inhibited the radiation-induced upregulation of Bcl-2 and Bcl-XL. The expression of survivin and XIAP was slightly increased by X irradiation, but were also inhibited by purvalanol A. On the other hand, pro-apoptotic protein, Bax, was not increased by X irradiation but slightly decreased by purvalanol A. Total RNA synthesis was inhibited by purvalanol A and as a consequence, the expression of mRNA of survivin, Bcl-XL and Bcl-2 was inhibited. These results indicated that purvalanol A sensitized radiation-induced apoptosis through the abrogation of G2 checkpoint and the downregulation of anti-apoptotic proteins by the inhibition of RNA synthesis. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 13th International Congress of Radiation Research | |||||
| 発表年月日 | ||||||
| 日付 | 2007-07-12 | |||||
| 日付タイプ | Issued | |||||
