{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:45:08Z","timestamp":1781109908187,"version":"3.54.1"},"reference-count":21,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,4,15]]},"abstract":"<jats:p>\n                    The majority of available antiandrogens have been reported to possess agonist activity to induce prostate-specific antigen, which might result in antiandrogen withdrawal syndrome. Here we report the identification of 3\u03b2-acetoxyandrost-1,5-diene-17-ethylene ketal (ADEK) from dehydroepiandrosterone metabolites and derivatives as a potent antiandrogen. We found ADEK could interrupt androgen binding to the androgen receptor (AR) and suppress androgen-induced transactivations of WT AR and a mutant AR in prostate cancer cells. ADEK inhibited prostate-specific antigen expression as well as growth in LNCaP prostate cancer cells stimulated by androgen. Importantly, ADEK had only marginal agonist effects, as compared with commonly used antiandrogens such as hydroxyflutamide and bicalutamide, leading to a lower possibility of inducing withdrawal response. Moreover, ADEK could block an adrenal androgen androstenediol-induced AR transactivation that hydroxyflutamide and bicalutamide failed to block. These unique antiandrogenic activities make ADEK a potential therapeutic compound that might be able to inhibit AR-mediated prostate cancer progression. Further\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies might facilitate the development of a better antiandrogen for the treatment of prostate cancer.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0831001100","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T18:56:03Z","timestamp":1050432963000},"page":"4440-4444","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":14,"title":["3\u03b2-Acetoxyandrost-1,5-diene-17-ethylene ketal functions as a potent antiandrogen with marginal agonist activity"],"prefix":"10.1073","volume":"100","author":[{"given":"Hiroshi","family":"Miyamoto","sequence":"first","affiliation":[{"name":"George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology, and The Cancer Center, University of Rochester, Rochester, NY 14642; and Institute for Enzyme Research, Department of Biochemistry, University of Wisconsin, Madison, WI 53726"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padma","family":"Marwah","sequence":"additional","affiliation":[{"name":"George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology, and The Cancer Center, University of Rochester, Rochester, NY 14642; and Institute for Enzyme Research, Department of Biochemistry, University of Wisconsin, Madison, WI 53726"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Marwah","sequence":"additional","affiliation":[{"name":"George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology, and The Cancer Center, University of Rochester, Rochester, NY 14642; and Institute for Enzyme Research, Department of Biochemistry, University of Wisconsin, Madison, WI 53726"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Lardy","sequence":"additional","affiliation":[{"name":"George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology, and The Cancer Center, University of Rochester, Rochester, NY 14642; and Institute for Enzyme Research, Department of Biochemistry, University of Wisconsin, Madison, WI 53726"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chawnshang","family":"Chang","sequence":"additional","affiliation":[{"name":"George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology, and The Cancer Center, University of Rochester, Rochester, NY 14642; and Institute for Enzyme Research, Department of Biochemistry, University of Wisconsin, Madison, WI 53726"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,4,2]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"293","volume":"1","author":"Huggins C","year":"1941","unstructured":"C Huggins, C V Hodges Cancer Res 1, 293\u2013297 (1941).","journal-title":"Cancer Res"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.52.3.154"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.52.1.23"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(01)01237-7"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0094-0143(05)70389-X"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0045(199609)29:3<153::AID-PROS2990290303>3.0.CO;2-5"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(98)00354-9"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.2990140204"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(05)80067-1"},{"key":"e_1_3_3_10_2","first-page":"1541","volume":"7","author":"Culig Z","year":"1993","unstructured":"Z Culig, A Hobisch, M V Cronauer, A C B Cato, A Hittmair, C Radmayr, J Eberle, G Bartsch, H Klocker Mol Endocrinol 7, 1541\u20131550 (1993).","journal-title":"Mol Endocrinol"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)61756-4"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.13.7379"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.19.11083"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.11173"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.11.5517"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108312200"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.5.8612526"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-2042.2000.00129.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910420622"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-62-5-812"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.1988.tb13971.x"}],"updated-by":[{"DOI":"10.1073\/pnas.1232068100","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2003,5,15]],"date-time":"2003-05-15T00:00:00Z","timestamp":1052956800000}}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0831001100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T17:40:52Z","timestamp":1649785252000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0831001100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,4,2]]},"references-count":21,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2003,4,15]]}},"alternative-id":["10.1073\/pnas.0831001100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0831001100","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,4,2]]},"assertion":[{"value":"2003-02-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-04-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}