{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:36:54Z","timestamp":1762864614024},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2003,4,4]],"date-time":"2003-04-04T00:00:00Z","timestamp":1049414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2003,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Vitamin D has been suggested as a chemopreventive and therapeutic modality for prostate cancer. However, hypercalcemic toxicity has limited the use of 1\u03b1,25\u2010dihydroxyvitamin D<jats:sub>3<\/jats:sub> (1,25\u2010(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>) in clinical trials, prompting the search for analogs of vitamin D with less toxicity while retaining efficacy as a modality for cancer intervention. In this study, the less hypercalcemic vitamin D analog 1\u03b1,24\u2010dihydroxyvitamin D<jats:sub>2<\/jats:sub> (1,24\u2010(OH)<jats:sub>2<\/jats:sub>D<jats:sub>2<\/jats:sub>) was examined for its effects on cellular growth inhibition and differentiation induction in the LNCaP human prostate carcinoma cell line.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>LNCaP cell growth was determined by quantifying DNA levels. Protein levels were determined using the ELISA method and immunoblotting. Levels of mRNA were determined using real\u2010time quantitative reverse transcriptase PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>LNCaP growth was decreased 50% by exposure to 0.01 nM 1,24\u2010(OH)<jats:sub>2<\/jats:sub>D<jats:sub>2<\/jats:sub> after 96 hr in the presence of a growth stimulatory 0.1 nM dose of the androgen R1881. Prostate specific antigen (PSA) levels were increased 3.5\u2010fold with 10 nM 1,24\u2010(OH)<jats:sub>2<\/jats:sub>D<jats:sub>2<\/jats:sub> treatment compared to a 1.9\u2010fold increase in PSA levels found with 10 nM 1,25\u2010(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> under low androgen conditions. Neither 1,24\u2010(OH)<jats:sub>2<\/jats:sub>D<jats:sub>2<\/jats:sub> nor 1,25\u2010(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> affected the expression of cytokeratin 18 protein levels. Treatment with 10 nM 1,24\u2010(OH)<jats:sub>2<\/jats:sub>D<jats:sub>2<\/jats:sub> alone produced a 1.3\u2010fold increase in AR mRNA and a 2.2\u2010fold increase in AR protein levels after 96 hr. Surprisingly, the addition of 1.0 nM R1881 alone or in combination with 10 nM 1,24\u2010(OH)<jats:sub>2<\/jats:sub>D<jats:sub>2<\/jats:sub> produced an approximately 60% decrease in AR mRNA, whereas AR protein levels were increased 1.6\u2010fold.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, 1,24\u2010(OH)<jats:sub>2<\/jats:sub>D<jats:sub>2<\/jats:sub> was found to be at least as effective as 1,25\u2010(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> at inhibiting growth and inducing differentiation markers in LNCaP prostate carcinoma cells and may thus prove useful in prostate cancer treatment. Prostate 55: 159\u2013167, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.10219","type":"journal-article","created":{"date-parts":[[2003,4,8]],"date-time":"2003-04-08T10:02:55Z","timestamp":1049796175000},"page":"159-167","source":"Crossref","is-referenced-by-count":25,"title":["Growth inhibition and differentiation in human prostate carcinoma cells induced by the vitamin D analog 1\u03b1,24\u2010dihydroxyvitamin D<sub>2<\/sub>"],"prefix":"10.1002","volume":"55","author":[{"given":"Joshua A.","family":"Bauer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd A.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawn R.","family":"Church","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric A.","family":"Ariazi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Wilding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,4,4]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.49.1.8"},{"key":"e_1_2_1_3_2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/j.1742-1241.1996.tb10036.x","article-title":"Recent advances in the medical management of prostate cancer","volume":"50","author":"Kirby KS","year":"1996","journal-title":"Br J Clin Pract"},{"key":"e_1_2_1_4_2","first-page":"1307","article-title":"Is vitamin D deficiency a risk factor for prostate cancer?","volume":"10","author":"Schwartz GG","year":"1990","journal-title":"Anticancer Res"},{"key":"e_1_2_1_5_2","first-page":"4014","article-title":"Sunlight\u2014Can it prevent as well as cause 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