{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T15:25:30Z","timestamp":1778253930745,"version":"3.51.4"},"reference-count":70,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["R21CA263290"],"award-info":[{"award-number":["R21CA263290"]}]},{"DOI":"10.13039\/100006952","name":"The Louisiana Board of Regents","doi-asserted-by":"crossref","award":["LEQSF-2023-24-ENH-DE-26"],"award-info":[{"award-number":["LEQSF-2023-24-ENH-DE-26"]}],"id":[{"id":"10.13039\/100006952","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Molecules"],"abstract":"<jats:p>Elevated cholesterol levels play important mitogenic roles. Pseurotin A (PsA) is a fermentation product that has recently been reported as a dual inhibitor of proprotein convertase subtilisin\/kexin type 9 (PCSK9) secretion and protein-protein interaction (PPI) with the LDLR. PsA showed a high acute safety profile and therapeutic potential against metastatic castration-resistant prostate cancer (mCRPC). The study aims to uncover the chronic safety, distribution, and anti-mCRPC genomic and molecular mechanistic insights of PsA. A 90-day chronic safety assessment of PsA up to 80 mg\/kg in Swiss albino mice showed no signs of hematological, biochemical, or major organ toxicity. PsA demonstrated rapid intravenous distribution and elimination in Swiss albino mice. PsA is biodistributed to multiple key organs but was not detected in the brain, indicating its inability to cross the blood-brain barrier. PsA effectively suppressed the recurrence of nude mice xenografted mCRPC, which was subjected to a neoadjuvant docetaxel and enzalutamide regimen, followed by surgical excision. Collected PsA and vehicle control-treated recurrent tumors were subjected to RNA-sequencing and pathway enrichment analysis (PEA) of differentially expressed genes (DEGs). PsA-treated tumors revealed multiple significantly enriched pathways associated with promoting tumor apoptosis and inhibiting both invasion and migration. The PPI network analyses for the downregulated DEGs displayed prominent networks of genes associated with the ubiquitin-proteasome system. Results provide comprehensive mechanistic and preclinical validations for PsA\u2019s potential as a novel PC recurrence suppressive lead entity.<\/jats:p>","DOI":"10.3390\/molecules30193963","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T15:07:48Z","timestamp":1759417668000},"page":"3963","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety, Pharmacokinetics, Translational and Molecular Mechanistic Insights on the Prostate Cancer Recurrence Suppressor Pseurotin A"],"prefix":"10.3390","volume":"30","author":[{"given":"Oliver C.","family":"McGehee","sequence":"first","affiliation":[{"name":"Department of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9057-4582","authenticated-orcid":false,"given":"Hassan Y.","family":"Ebrahim","sequence":"additional","affiliation":[{"name":"Department of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"},{"name":"Department of Biomedical Sciences, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine, Monroe, LA 71203, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nehal A.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8200-4616","authenticated-orcid":false,"given":"Chandra Mohan Reddy","family":"Muthumula","sequence":"additional","affiliation":[{"name":"Department of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalal","family":"Dawud","sequence":"additional","affiliation":[{"name":"Department of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-4275","authenticated-orcid":false,"given":"Judy A.","family":"King","sequence":"additional","affiliation":[{"name":"DeBusk College of Osteopathic Medicine, Lincoln Memorial University, 9737 Cogdill Road, Knoxville, TN 37932, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amal","family":"Kaddoumi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, 1201 Goss Lane, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1456-4064","authenticated-orcid":false,"given":"Khalid A.","family":"El Sayed","sequence":"additional","affiliation":[{"name":"Department of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"Cancer Statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. 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