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Consequently, we investigated the potential of \u03b2\u2010sitosterol and the synthetic derivative <jats:bold>2<\/jats:bold> as potent inhibitors of androgen synthesis, a critical process for the growth and survival of prostate tumor LNCaP cells. Solubilized LNCaP microsomes were used as a source of SRD5A1 and AKR1C3 to monitor androgen synthesis from labeled androstenedione, both in the presence and absence of \u03b2\u2010sitosterol or <jats:bold>2<\/jats:bold>. Furthermore, the effect of these steroids on LNCaP viability was determined using the MTT method. Our findings revealed significant insights into the androgen synthesis pathways in LNCaP cells. The most efficient metabolic route for dihydrotestosterone formation was the conversion of androstenedione to 5\u03b1\u2010androstanedione rather than from testosterone in LNCaP. This conclusion is supported by the Vmax values for 5\u03b1\u2010androstanedione formation (271.05\u2009\u00b1\u20095.0\u2009ng\/mg protein\/min) and the Vmax of testosterone formation (80.1\u2009\u00b1\u20098.0\u2009ng\/mg protein\/min). Both \u03b2\u2010sitosterol and <jats:bold>2<\/jats:bold> demonstrated substantial inhibitory effects of these enzymes for dihydrotestosterone formation and significantly reduced cell viability, highlighting their therapeutic potential. These findings enhance our understanding of the inhibitory effects of \u03b2\u2010sitosterol and <jats:bold>2<\/jats:bold> on LNCaP cells and suggest their promising application in the treatment of prostate cancer.<\/jats:p>","DOI":"10.1002\/ddr.70078","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T22:05:24Z","timestamp":1742940324000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of Steroidogenesis in Prostate Cancer Cells by Both a Natural and Another Synthetic Steroid"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5096-8840","authenticated-orcid":false,"given":"Marisa","family":"Cabeza","sequence":"first","affiliation":[{"name":"Departamento de Sistemas Biol\u00f3gicos y de Producci\u00f3n Agr\u00edcola y Animal Universidad Aut\u00f3noma Metropolitana\u2010Xochimilco Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karla","family":"Mej\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Sistemas Biol\u00f3gicos y de Producci\u00f3n Agr\u00edcola y Animal Universidad Aut\u00f3noma Metropolitana\u2010Xochimilco Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Sistemas Biol\u00f3gicos y de Producci\u00f3n Agr\u00edcola y Animal Universidad Aut\u00f3noma Metropolitana\u2010Xochimilco Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivonne","family":"Heuze","sequence":"additional","affiliation":[{"name":"Departamento de Sistemas Biol\u00f3gicos y de Producci\u00f3n Agr\u00edcola y Animal Universidad Aut\u00f3noma Metropolitana\u2010Xochimilco Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Morales\u2010Pacheco","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncogen\u00f3mica, Instituto Nacional de Medicina Gen\u00f3mica Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauricio","family":"Rodr\u00edguez\u2010Dorantes","sequence":"additional","affiliation":[{"name":"Laboratorio de Oncogen\u00f3mica, Instituto Nacional de Medicina Gen\u00f3mica Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14081711"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008469-200112000-00005"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6882-10-24"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-007-9070-7"},{"key":"e_1_2_9_6_1","first-page":"153","article-title":"Effect of Beta\u2010Sitosterol as Inhibitor of 5 Alpha\u2010Reductase in Hamster Prostate","volume":"46","author":"Cabeza M.","year":"2003","journal-title":"Proceedings of the Western Pharmacology Society"},{"key":"e_1_2_9_7_1","first-page":"17","article-title":"\u03b2\u2010Sitosterol as a Competitive Inhibitor of the Human Type 2 5\u03b1\u2010 Reductase","volume":"11","author":"Cabeza V. 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