{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:33Z","timestamp":1787028573414,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metastatic castration-resistant prostate cancer\/PCa (mCRPC) is a clinically advanced form of PCa that is associated with increased aggressiveness, cancer stemness, morbidity, and the risk of developing resistance to taxanes, currently the first-line chemotherapy for mCRPC. Clofazimine (CLF) is a potential immunomodulator drug that is FDA-approved for the treatment of leprosy. Recently, using in vitro, in vivo, and ex vivo models, we established the efficacy of CLF in chronic myeloid leukemia and multiple myeloma. Here, we demonstrate that CLF is effective as a single agent and in combination with taxanes in a panel of cell lines representing the diversity of CRPC patients. Using a microfluidic assay, we showed the impact of CLF on cancer cell migration and metastatic potential. Further, we also found that CLF reduces ALDH activity\u2014a marker for cancer \u2018stem-like\u2019 cells (CSCs), a subtype of cancer cells with self-renewal and differentiation capacities (epithelial-to-mesenchymal transdifferentiation\/EMT). Bulk and single-cell RNAseq followed by functional validation and in silico analysis showed that CLF treatment is associated with apoptosis, ER stress, oxidative phosphorylation, and mitochondrial dysfunction. Most importantly, CLF modulates the expression of several non-coding RNAs, including MALAT1 and NEAT1, that are linked to tumor cell proliferation, cell migration, and drug resistance.<\/jats:p>","DOI":"10.3390\/ijms262210892","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T13:51:08Z","timestamp":1762782668000},"page":"10892","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clofazimine Treatment Modulates Key Non-Coding RNAs Associated with Tumor Progression and Drug Resistance in Lethal Prostate Cancer"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9854-9091","authenticated-orcid":false,"given":"Sarah","family":"Batten","sequence":"first","affiliation":[{"name":"Department of Drug Discovery & Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery & Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA"},{"name":"Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0785-8312","authenticated-orcid":false,"given":"Jeremiah","family":"Pfitzer","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery & Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Chinedu","family":"Nweze","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Samuel Ginn College of Engineering, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Mazumder","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery & Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA"},{"name":"Center for Pharmacogenomics and Single-Cell Omics Initiative, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6143-3991","authenticated-orcid":false,"given":"Robert D.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery & Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8069-3278","authenticated-orcid":false,"given":"Panagiotis","family":"Mistriotis","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Samuel Ginn College of Engineering, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taraswi","family":"Mitra Ghosh","sequence":"additional","affiliation":[{"name":"Department of Urology, Mass General Brigham and Women\u2019s Hospital, 1529 Thorn Research Building, 20 Shattuck Street, Boston, MA 02115, USA"},{"name":"Department of Surgery, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4046-7070","authenticated-orcid":false,"given":"Amit Kumar","family":"Mitra","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery & Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA"},{"name":"Center for Pharmacogenomics and Single-Cell Omics Initiative, Auburn University, Auburn, AL 36849, 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