{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T01:22:26Z","timestamp":1777512146113,"version":"3.51.4"},"reference-count":65,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Prostate cancer remains a major contributor to cancer-related morbidity and mortality worldwide, emphasizing the need for safer and more effective therapeutic options. Andrographolide, a diterpenoid lactone derived from Andrographis paniculata, has shown promising anticancer activity, yet its effects on microRNA (miRNA) regulation in prostate cancer remain insufficiently explored. Methods: In this study, we evaluated the cytotoxic and molecular effects of andrographolide on two human prostate cancer cell lines, PC3 and LNCaP, along with HEK-293 cells as a noncancerous model. Results: Cell viability assessment using the MTT assay revealed dose-dependent cytotoxicity, with 24 h IC50 values of 82.31 \u00b5M for PC3, 68.79 \u00b5M for LNCaP, and 133.9 \u00b5M for HEK-293 cells. Subsequent expression analysis of key oncogenic and tumor suppressor miRNAs demonstrated that andrographolide induced the upregulation of miR-16-5p, miR-34a-5p, and miR-200a-5p miRNAs implicated in apoptosis, proliferation control, and androgen receptor signaling. In contrast, the expression of oncomiRs miR-21-5p and miR-221-5p showed minimal or nonsignificant changes, reflecting the complex and context-specific roles of miRNAs in prostate cancer. Gene expression profiling further indicated differential transcriptional responses between the two prostate cancer cell lines, consistent with their distinct molecular backgrounds. Conclusions: Although HEK-293 cytotoxicity and previously reported nephrotoxic effects warrant caution, these results support the potential of andrographolide as an adjuvant phytochemical capable of modulating clinically relevant miRNAs in prostate cancer. Future studies investigating optimized delivery systems and validating direct miRNA targets may help advance andrographolide toward safer and more targeted therapeutic applications.<\/jats:p>","DOI":"10.3390\/genes16121514","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T10:41:23Z","timestamp":1765968083000},"page":"1514","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differential Expression of Key Oncogenic and Tumor Suppressor MicroRNAs Induced by Andrographolide in Androgen-Independent PC3 and Androgen-Dependent LNCaP Prostate Cancer Cells"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5052-4019","authenticated-orcid":false,"given":"Padmavati","family":"Sahare","sequence":"first","affiliation":[{"name":"Institute of Advanced Materials for Sustainable Manufacturing, Tecnologico de Monterrey, Campus Queretaro, Queretaro 76130, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6342-4842","authenticated-orcid":false,"given":"Luis Alberto","family":"Bravo-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"School of Engineering and Sciences, Tecnologico de Monterrey, Campus Queretaro, Queretaro 76130, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2087-9559","authenticated-orcid":false,"given":"Diego Antonio","family":"Veloz-Briones","sequence":"additional","affiliation":[{"name":"School of Engineering and Sciences, Tecnologico de Monterrey, Campus Queretaro, Queretaro 76130, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2186-9984","authenticated-orcid":false,"given":"Daniela","family":"Bernal-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"School of Engineering and Sciences, Tecnologico de Monterrey, Campus Queretaro, Queretaro 76130, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8026-2022","authenticated-orcid":false,"given":"Ignacio","family":"Bola\u00f1os-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"School of Engineering and Sciences, Tecnologico de Monterrey, Campus Queretaro, Queretaro 76130, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7744-8685","authenticated-orcid":false,"given":"Brenda","family":"Anguiano","sequence":"additional","affiliation":[{"name":"Instituto de Neurobiolog\u00eda, Universidad Nacional Autonoma de Mexico, Campus UNAM 3001, Juriquilla 76230, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1162-6928","authenticated-orcid":false,"given":"Gabriel","family":"Luna-B\u00e1rcenas","sequence":"additional","affiliation":[{"name":"Institute of Advanced Materials for Sustainable Manufacturing, Tecnologico de Monterrey, Campus Queretaro, Queretaro 76130, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5024-7261","authenticated-orcid":false,"given":"Sujay","family":"Paul","sequence":"additional","affiliation":[{"name":"School of Engineering and Sciences, Tecnologico de Monterrey, Campus Queretaro, Queretaro 76130, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"ref_1","first-page":"e48252","article-title":"An In-Depth Look Into the Epidemiological and Etiological Aspects of Prostate Cancer: A Literature Review","volume":"15","author":"Salameh","year":"2023","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tzelepi, V. 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