{"created":"2023-05-15T14:50:29.251079+00:00","id":69044,"links":{},"metadata":{"_buckets":{"deposit":"c5f5c504-2a6f-40a8-b66f-8085425ae5bd"},"_deposit":{"created_by":1,"id":"69044","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"69044"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00069044","sets":["10:28"]},"author_link":["677644","677645","677646"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2007-07-12","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"[Purpose]\nIonizing 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\\n[Materials and Methods]\nHuman 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\\n[Results and Discussion]\nCotreatment 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.","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"13th International Congress of Radiation Research","subitem_description_type":"Other"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Iizuka, Daisuke"}],"nameIdentifiers":[{"nameIdentifier":"677644","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"et.al"}],"nameIdentifiers":[{"nameIdentifier":"677645","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"飯塚 大輔","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"677646","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"Enhancement of radiation-induced cell killing by inhibiting G2 checkpoint with purvalanol A.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Enhancement of radiation-induced cell killing by inhibiting G2 checkpoint with purvalanol A."}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2007-07-20"},"publish_date":"2007-07-20","publish_status":"0","recid":"69044","relation_version_is_last":true,"title":["Enhancement of radiation-induced cell killing by inhibiting G2 checkpoint with purvalanol A."],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T20:19:09.047065+00:00"}