{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T01:33:20Z","timestamp":1788744800516,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CHDE S.A., Rzesz\u00f3w, Poland","award":["037200"],"award-info":[{"award-number":["037200"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pancreatic cancer (PC) is an aggressive malignancy with a poor prognosis, requiring innovative approaches to evaluate new therapies. Considering the high activity of unsymmetrical bisacridines (UAs) in PC monolayer cultures, we employed multicellular tumor spheroids (MCTS) to assess whether UAs retain pro-apoptotic activity under more physiologically relevant conditions. Ultra-low attachment plates were used to form spheroids from three PC cell lines (Panc-1, MIA PaCa-2, and AsPC-1) with different genotypes and phenotypes. The effects of UA derivatives (C-2028, C-2045, and C-2053) were evaluated using microscopy and flow cytometry (7-AAD for viability and annexin V-FITC\/PI for membrane integrity). UAs altered the morphology of the spheroids and reduced their growth. Notably, Panc-1 spheroids exhibited compromised integrity. The increase in 7-AAD+ cells confirmed diminished cell viability, and annexin V-FITC assays showed apoptosis as the dominant death pathway. Interestingly, the exact derivative was most active against a given cell line regardless of culture conditions. These results confirm that UAs maintain anticancer activity in 3D cultures and induce apoptosis, with varying efficacy across different cell lines. This underscores the value of diverse cellular models in compound evaluation and supports UAs as promising candidates for pancreatic cancer therapy.<\/jats:p>","DOI":"10.3390\/ijms26157557","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T07:45:11Z","timestamp":1754466311000},"page":"7557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Pro-Apoptotic Effects of Unsymmetrical Bisacridines in 3D Pancreatic Multicellular Tumor Spheroids"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6650-2738","authenticated-orcid":false,"given":"Agnieszka","family":"Kurdyn","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gda\u0144sk University of Technology, Gabriela Narutowicza Str. 11\/12, 80-233 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Paluszkiewicz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gda\u0144sk University of Technology, Gabriela Narutowicza Str. 11\/12, 80-233 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-021X","authenticated-orcid":false,"given":"Ewa","family":"Augustin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gda\u0144sk University of Technology, Gabriela Narutowicza Str. 11\/12, 80-233 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"688","DOI":"10.20892\/j.issn.2095-3941.2019.0252","article-title":"The Challenge of Drug Resistance in Pancreatic Ductal Adenocarcinoma: A Current Overview","volume":"16","author":"Mesas","year":"2019","journal-title":"Cancer Biol. 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