{"created":"2023-06-19T07:25:33.574488+00:00","id":13455,"links":{},"metadata":{"_buckets":{"deposit":"8113eb7a-0ee5-4fa9-a92f-99cbb697f7f9"},"_deposit":{"created_by":61,"id":"13455","owners":[61],"pid":{"revision_id":0,"type":"depid","value":"13455"},"status":"published"},"_oai":{"id":"oai:gifu-pu.repo.nii.ac.jp:00013455","sets":["212:259","212:259:315"]},"author_link":["21784","21785","21788","21786","21783","21789","21787"],"item_10003_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2017","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"4","bibliographicPageEnd":"290","bibliographicPageStart":"279","bibliographicVolumeNumber":"34","bibliographic_titles":[{},{"bibliographic_title":"Cell Biology and Toxicology","bibliographic_titleLang":"en"}]}]},"item_10003_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"We recently demonstrated the cytotoxic action of a novel phenformin derivative, 2-(2-chlorophenyl)ethylbiguanide (2-Cl-Phen), on HT-29 cells under a serum- and glucose-deprived condition. In that study, we showed that the ATF6 arm of the ER stress pathway and c-Myc expression were downregulated 12 h after the treatment with 2-Cl-Phen. Through characterization of intracellular events at the early phase of the 2-Cl-Phen treatment before noticeable morphological changes, we found rapid fluctuations in the c-Myc and ATF4 proteins but not in their mRNAs in 2-Cl-Phen-treated HT-29 cells under the serum- and glucose-deprived condition. The 2-Cl-Phen-mediated downregulation of ATF4 protein was not paralleled by the phosphorylation status of PERK and eIF2α. Reduction of c-Myc expression by 2-Cl-Phen was more profound than that of ATF4 expression, and phosphorylated c-Myc was downregulated within 2 h. Pharmacological studies on the expression of c-Myc and ATF4 proteins showed that this decrease was mediated through proteasomal degradation but not by autophagy. Interestingly, treatment with lithium chloride, which is a well-known inhibitor of GSK3β, partially recovered the expression of ATF4 protein, but its effect on the level of total c-Myc protein was negligible. Treatment with 2-Cl-Phen increased the expression of phosphorylated AMPK, but Compound C, an AMPK inhibitor, did not influence the expression of c-Myc protein in HT-29 cells. Finally, we observed that 2-Cl-Phen partially attenuated the gene expression of integrin subunit α1 (ITGA1), a downstream target of c-Myc. Taken together, these results show that 2-Cl-Phen rapidly downregulated the expression of c-Myc in addition to ER stress responses in a post-translational manner. Further elucidation and improvement of this multi-target-directed compound will provide new insights for developing therapeutic strategies against cancer.","subitem_description_type":"Abstract"}]},"item_10003_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1007/s10565-017-9410-0","subitem_relation_type_select":"DOI"}}]},"item_10003_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0742-2091","subitem_source_identifier_type":"ISSN"}]},"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":"Oh-hashi, Kentaro"}],"nameIdentifiers":[{"nameIdentifier":"21783","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Matsumoto, Shiori"}],"nameIdentifiers":[{"nameIdentifier":"21784","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sakai, Takayuki"}],"nameIdentifiers":[{"nameIdentifier":"21785","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nomura, Yuki"}],"nameIdentifiers":[{"nameIdentifier":"21786","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Okuda, Kensuke"}],"nameIdentifiers":[{"nameIdentifier":"21787","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nagasawa, Hideko"}],"nameIdentifiers":[{"nameIdentifier":"21788","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hirata, Yoko"}],"nameIdentifiers":[{"nameIdentifier":"21789","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 paper","resourceuri":"http://purl.org/coar/resource_type/c_5794"}]},"item_title":"Elucidating the rapid action of 2-(2-chlorophenyl)ethylbiguanide on HT-29 cells under a serum- and glucose-deprived condition","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Elucidating the rapid action of 2-(2-chlorophenyl)ethylbiguanide on HT-29 cells under a serum- and glucose-deprived condition","subitem_title_language":"en"}]},"item_type_id":"10003","owner":"61","path":["259","315"],"pubdate":{"attribute_name":"公開日","attribute_value":"2019-03-04"},"publish_date":"2019-03-04","publish_status":"0","recid":"13455","relation_version_is_last":true,"title":["Elucidating the rapid action of 2-(2-chlorophenyl)ethylbiguanide on HT-29 cells under a serum- and glucose-deprived condition"],"weko_creator_id":"61","weko_shared_id":-1},"updated":"2023-06-19T08:48:17.726603+00:00"}