{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:00:54Z","timestamp":1787695254016,"version":"build-2784847793"},"reference-count":40,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Lercanidipine is a third-generation dihydropyridine calcium channel blocker. In addition to their well-established cardiovascular effects, calcium channel blockers are increasingly recognized for their therapeutic potential in various cancers. This study aimed to investigate the potential anticancer effects of lercanidipine on cancer cell lines\u2014particularly in combination with cisplatin\u2014by assessing parameters such as cell viability (MTT assay), proliferation, MAPK pathway activity, caspase enzyme levels, and TNF-\u03b1 expression. Methods: In this study, the effects of lercanidipine, both alone and in combination with cisplatin, on cell viability were evaluated using the MTT assay in MCF-7, SH-SY5Y, PC3, and HEK293 cell lines. To assess intracellular signaling and apoptotic pathways, MAPK inhibition, as well as caspase-3 and caspase-8 activities, were measured using ELISA. Additionally, to evaluate the anti-inflammatory potential, TNF-\u03b1 levels in LPS-stimulated RAW264.7 cells were analyzed via. Results: The study revealed that lercanidipine showed significant cytotoxic effects, particularly in SH-SY5Y and PC3 cancer cell lines, while it did not induce a 50% loss of viability in healthy HEK293 cells. When combined with cisplatin, lercanidipine enhanced cytotoxicity by 2.7-fold in neuroblastoma (SH-SY5Y) cells, 1.6-fold in breast cancer (MCF7) cells, and 1.9-fold in prostate cancer (PC3) cells. MAPK activity was inhibited by 83.6% at 20 \u03bcM lercanidipine, while dose-dependent increases in caspase-3 and caspase-8 activities were observed. Additionally, lercanidipine decreased TNF-\u03b1 levels in LPS-stimulated RAW264.7 cells, indicating its potential anti-inflammatory effect. Conclusions: In conclusion, lercanidipine demonstrated selective anticancer effects in cancer cell lines and showed synergistic cytotoxicity when combined with cisplatin. It also significantly inhibited MAPK signaling, activated apoptotic caspases, and reduced TNF-\u03b1 levels, suggesting potential anti-inflammatory activity. These findings highlight lercanidipine\u2019s potential for repurposing as an adjunct in cancer therapy.<\/jats:p>","DOI":"10.3390\/ph18050651","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T11:35:13Z","timestamp":1746185713000},"page":"651","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lercanidipine Enhances Cisplatin Activity: Dual Anticancer and Anti-Inflammatory Effects via Caspase Activation and MAPK Inhibition"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6626-4859","authenticated-orcid":false,"given":"Tugce","family":"Uskur","sequence":"first","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine, K\u0131rklareli University, K\u0131rklareli 39100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1896-2729","authenticated-orcid":false,"given":"Sevde Nur","family":"Biltekin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology, School of Pharmacy, Istanbul Medipol University, \u0130stanbul 34810, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gokhan","family":"Faikoglu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Okan University, \u0130stanbul 34959, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kubra","family":"Saygisever-Faikoglu","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine, Cerrahpasa-Istanbul University, \u0130stanbul 34098, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bark\u0131n","family":"Berk","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Okan University, \u0130stanbul 34959, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1111\/j.1742-1241.2006.01176.x","article-title":"Lercanidipine is an effective and well tolerated antihypertensive drug regardless the cardiovascular risk profile: The LAURA study","volume":"60","author":"Barrios","year":"2006","journal-title":"Int. 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