{"created":"2023-06-19T11:23:19.371802+00:00","id":3841,"links":{},"metadata":{"_buckets":{"deposit":"abb7fe5d-6008-4636-8601-40fbfd9d31ab"},"_deposit":{"created_by":3,"id":"3841","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"3841"},"status":"published"},"_oai":{"id":"oai:asahikawa-med.repo.nii.ac.jp:00003841","sets":["7","7:24"]},"author_link":["11421","11422","11423","11424","11425","11426","11427","11428","11429","11430","11431","11432"],"control_number":"3841","item_1716186501932":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"22181812","subitem_relation_type_select":"PMID"}}]},"item_5_biblio_info_21":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2012-04-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"4","bibliographicPageEnd":"774","bibliographicPageStart":"767","bibliographicVolumeNumber":"103","bibliographic_titles":[{"bibliographic_title":"Cancer Science"}]}]},"item_5_description_33":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Hypoxia inducible factor-1α (HIF-1α) has a central role in cellular oxygen-sensing, and its overexpression in many types of cancer is considered important in tumor progression. Thus, targeting HIF-1α production and activity has been of great therapeutic interest. In normoxic conditions, HIF-1α is hydroxylated by oxygen-dependent prolyl-hydroxylases, which require ferrous iron for its activity. The tumor suppressor protein von Hippel Lindau binds to the hydroxylated HIF-1α, which is then ubiquitinated and degraded by proteasomes. We focused on the physiological degradation machinery of HIF-1α mediated by prolyl hydroxylases. Previously, we identified a small molecule, LS081, that is capable of stimulating iron uptake into cells. In the present study, we aimed to inhibit the expression of HIF-1α protein and growth of hepatocellular carcinoma by using the iron-facilitating activity of LS081. In the human hepatocellular carcinoma cell lines Hep3B and HepG2, a combination of LS081 and ferric ammonium citrate (LS081/FeAC) inhibited HIF-1α protein expression but did not inhibit HIF-1α mRNA expression. A mutated HIF-1α protein, which has proline residues that were replaced with alanine and transfected into HEK293 cells, was not affected by the combination of LS081 and FeAC. Furthermore, the iron-facilitating activity of LS081 resulted in Hep3B and HepG2 growth inhibition in vitro and in vivo. These results indicate that the iron-facilitating activity of LS081 inhibits HIF-1α expression through prolyl-hydroxylation of HIF-1α and might have a therapeutic effect in the treatment of hepatocellular carcinoma.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_5_description_36":{"attribute_name":"注記","attribute_value_mlt":[{"subitem_description":"Author","subitem_description_type":"Other"}]},"item_5_description_37":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_description":"text","subitem_description_type":"Other"}]},"item_5_description_41":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_5_relation_24":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1111/j.1349-7006.2011.02192.x","subitem_relation_type_select":"DOI"}}]},"item_5_source_id_22":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1349-7006","subitem_source_identifier_type":"EISSN"}]},"item_5_text_44":{"attribute_name":"ID(XooNIps)","attribute_value_mlt":[{"subitem_text_value":"22181812"}]},"item_5_text_54":{"attribute_name":"閲覧数(XooNIps)","attribute_value_mlt":[{"subitem_text_value":"1107"}]},"item_5_text_55":{"attribute_name":"ダウンロード数(XooNIps)","attribute_value_mlt":[{"subitem_text_value":"1053"}]},"item_5_version_type_38":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"田中, 宏樹","creatorNameLang":"ja"},{"creatorName":"タナカ, ヒロキ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"11421","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhen, Li","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"11422","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Katsuya, Ikuta","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"11423","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Lynda, Addo","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"11424","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hiroaki, Akutsu","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"11425","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Masao, Nakamura","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"11426","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Katsunori, Sasaki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"11427","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Takaaki, Ohtake","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"11428","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Mikihiro, Fujiya","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"11429","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yoshihiro, Torimoto","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"11430","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Jonathan, Glass","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"11431","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yutaka, Kohgo","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"11432","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-07-06"}],"displaytype":"detail","filename":"4404.pdf","filesize":[{"value":"5.9 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"4404.pdf","url":"https://asahikawa-med.repo.nii.ac.jp/record/3841/files/4404.pdf"},"version_id":"02453a0f-cb67-405f-a9ae-578098be2a6a"}]},"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":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Iron facilitator LS081 reduces hypoxia-inducible factor-1α protein and functions as anticancer agent in hepatocellular carcinoma.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Iron facilitator LS081 reduces hypoxia-inducible factor-1α protein and functions as anticancer agent in hepatocellular carcinoma.","subitem_title_language":"en"}]},"item_type_id":"5","owner":"3","path":["6","7","24"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2012-05-14"},"publish_date":"2012-05-14","publish_status":"0","recid":"3841","relation_version_is_last":true,"title":["Iron facilitator LS081 reduces hypoxia-inducible factor-1α protein and functions as anticancer agent in hepatocellular carcinoma."],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2024-08-09T08:27:46.818683+00:00"}