{"created":"2023-06-19T07:26:20.263734+00:00","id":14738,"links":{},"metadata":{"_buckets":{"deposit":"b1a4951f-553a-497e-990d-884e80b75914"},"_deposit":{"created_by":159,"id":"14738","owners":[159],"pid":{"revision_id":0,"type":"depid","value":"14738"},"status":"published"},"_oai":{"id":"oai:gifu-pu.repo.nii.ac.jp:00014738","sets":["212:276:279"]},"author_link":["35868","35875","35871","35877","35869","35876","35866","35872","35873","35874","35878","35879","35867","35870","35864","35865"],"item_3_biblio_info_3":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"22","bibliographicPageStart":"14356","bibliographicVolumeNumber":"23","bibliographic_titles":[{},{"bibliographic_title":"International Journal of Molecular Sciences","bibliographic_titleLang":"en"}]}]},"item_3_textarea_2":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_textarea_value":"Prostate cancer (PC) represents the most common cancer disease in men. Since high levels of androgens increase the risk of PC, androgen deprivation therapy is the primary treatment; however this leads to castration-resistant PC (CRPC) with a poor prognosis. The progression to CRPC involves ectopic androgen production in the adrenal glands and abnormal activation of androgen signaling due to mutations and/or amplification of the androgen receptor (AR) as well as activation of androgen-independent proliferative pathways. Recent studies have shown that adrenal-derived 11-oxygenated androgens (11-ketotestosterone and 11-ketodihydrotestosterone) with potencies equivalent to those of traditional androgens (testosterone and dihydrotestosterone) are biomarkers of CRPC. Addnl., dehydrogenase/reductase SDR family member 11 (DHRS11) has been reported to be a 17β-hydroxysteroid dehydrogenase that catalyzes the production of the 11-oxygenated and traditional androgens. This study was conducted to evaluate the pathophysiol. roles of DHRS11 in PC using three LNCaP, C4-2 and 22Rv1 cell lines. DHRS11 silencing and inhibition resulted in suppression of the androgen-induced expression of AR downstream genes and decreases in the expression of nuclear AR and the proliferation marker Ki67, suggesting that DHRS11 is involved in androgen-dependent PC cell proliferation. We found that 5,7-dihydroxy-8-methyl-2-[2-(4-hydroxyphenyl)ethenyl]-4H-1-benzopyran-4-one (Kobochromone A, KC-A), an ingredient in the flowers of Carex kobomugi, is a novel potent DHRS11 inhibitor (IC50 = 0.35 μM). Addnl., KC-A itself decreased the AR expression in PC cells. Therefore, KC-A suppresses the androgen signaling in PC cells through both DHRS11 inhibition and AR downregulation. Furthermore, KC-A enhanced the anticancer activity of abiraterone, a CRPC drug, suggesting that it may be a potential candidate for the development of drugs for the prevention and treatment of CRPC."}]},"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_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Carex prostate cancer polyphenol androgen receptor antiandrogenic anticancer; Carex kobomugi; DHRS11; androgen receptor; polyphenol; prostate cancer","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"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":"Antiandrogenic Effects of a Polyphenol in Carex kobomugi through Inhibition of Androgen Synthetic Pathway and Downregulation of Androgen Receptor in Prostate Cancer Cell Lines","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Antiandrogenic Effects of a Polyphenol in Carex kobomugi through Inhibition of Androgen Synthetic Pathway and Downregulation of Androgen Receptor in Prostate Cancer Cell Lines","subitem_title_language":"en"}]},"item_type_id":"3","owner":"159","path":["279"],"pubdate":{"attribute_name":"公開日","attribute_value":"2023-03-10"},"publish_date":"2023-03-10","publish_status":"0","recid":"14738","relation_version_is_last":true,"title":["Antiandrogenic Effects of a Polyphenol in Carex kobomugi through Inhibition of Androgen Synthetic Pathway and Downregulation of Androgen Receptor in Prostate Cancer Cell Lines"],"weko_creator_id":"159","weko_shared_id":-1},"updated":"2023-06-19T07:39:50.281995+00:00"}