{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T20:45:08Z","timestamp":1777668308313,"version":"3.51.4"},"reference-count":38,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Due to its silent clinical progression and diagnosis often occurring at advanced stages, ovarian cancer continues to be a major contributor to gynecological cancer-related mortality worldwide. Recent evidence underscores the critical therapeutic value of targeting the interplay between DNA damage response pathways, particularly poly (ADP-ribose) polymerase 1 (PARP1), and mitogen-activated protein kinase (MAPK) signaling cascades.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we investigated the anti-cancer potential of the naturally derived small molecule usnic acid in a chemotherapy-resistant epithelial ovarian cancer model (SKOV-3 cells) at the cellular and molecular levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings demonstrate for the first time that usnic acid exerts a dual-pathway apoptotic mechanism by simultaneously inhibiting PARP1 and activating the MAPK signaling pathway. Remarkably, usnic acid mimics the gene-silencing action of siRNA on PARP1, suggesting a highly specific and potent inhibitory effect at the molecular level. Although ROS involvement and pathway causality were not directly tested, this dual-action profile enhances DNA damage-induced apoptosis and highlights usnic acid as a promising therapeutic candidate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The study presents a novel molecular framework in which a single small molecule can coordinate apoptosis through parallel regulatory pathways, demonstrating the potential for innovative therapeutic approaches in the treatment of aggressive and treatment-resistant ovarian cancers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09603271251409541","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T07:40:01Z","timestamp":1766389201000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Usnic Acid induces dual-pathway apoptosis in SKOV-3 ovarian cancer cells via PARP1 inhibition and MAPK pathway activation"],"prefix":"10.1177","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8260-7492","authenticated-orcid":false,"given":"Mehmet K\u00fcr\u015fat","family":"Derici","sequence":"first","affiliation":[{"name":"University of Health Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2197-1223","authenticated-orcid":false,"given":"Mine","family":"Ensoy","sequence":"additional","affiliation":[{"name":"Ankara University"},{"name":"Division of Pharmacy and Optometry, Faculty of Biology Medicine and Health, School of Health Science, University of Manchester, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7970-880X","authenticated-orcid":false,"given":"Pelin","family":"Mutlu","sequence":"additional","affiliation":[{"name":"Ankara University"},{"name":"Integrated Technologies Research Center (B\u00dcTAM), Ankara University, Ba\u011fl\u0131ca, Ankara, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5662-2333","authenticated-orcid":false,"given":"Demet","family":"Cansaran-Duman","sequence":"additional","affiliation":[{"name":"Ankara University"},{"name":"Integrated Technologies Research Center (B\u00dcTAM), Ankara University, Ba\u011fl\u0131ca, Ankara, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,12,21]]},"reference":[{"key":"e_1_3_6_2_2","first-page":"561","article-title":"Ovarian cancer: an overview","volume":"91","author":"Penny SM","year":"2020","unstructured":"Penny SM. Ovarian cancer: an overview. Radiol Technol 2020; 91: 561\u2013575.","journal-title":"Radiol Technol"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.4.110807.092246"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-023-00617-9"},{"key":"e_1_3_6_5_2","unstructured":"Kosani\u0107 M Rankovi\u0107 B Stanojkovi\u0107 T. Antioxidant antimicrobial and anticancer activity of 3 umbilicaria species. J Food Sci; 77: 20."},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4RA12340A"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2019.108898"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389201021666201002155955"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/2767-9764.CRC-23-0101"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-020-01644-5"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.24424"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.04.018"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aal5148"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","unstructured":"Sun L Li Y Wang M et al. p53 deficiency mediates cisplatin resistance by upregulating RRM2 and crotonylation of RRM2K283 through the downregulation of SIRT7. Front Mol Biosci; 11: 1423594. DOI: 10.3389\/fmolb.2024.1423594.","DOI":"10.3389\/fmolb.2024.1423594"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2023.5496"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2023.09.003"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290105"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","unstructured":"Guo Y Pan W Liu S et al. ERK\/MAPK signalling pathway and tumorigenesis (Review). Exp Ther Med. DOI: 10.3892\/etm.2020.8454 Epub ahead of print 15 January 2020.","DOI":"10.3892\/etm.2020.8454"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10102509"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/1947601910383418"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1089\/cbr.2016.2133"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.03.016"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom14101269"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010041"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.2174\/157340612802084225"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111336"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01347-1"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12102199"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2011.12.003"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-021-00355-1"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21072346"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt384"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.20517\/cdr.2019.10"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90579.2008"},{"key":"e_1_3_6_35_2","first-page":"100709","article-title":"Control of doxorubicin-induced, reactive oxygen-related apoptosis by glutathione peroxidase 1 in cardiac fibroblasts","volume":"21","author":"Doroshow JH","year":"2020","unstructured":"Doroshow JH, Esworthy RS, Chu F-F. Control of doxorubicin-induced, reactive oxygen-related apoptosis by glutathione peroxidase 1 in cardiac fibroblasts. Biochem Biophys Rep 2020; 21: 100709.","journal-title":"Biochem Biophys Rep"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s43042-024-00485-7"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1177\/0960327120930257"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12210-021-01044-7"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40659-020-00285-4"}],"container-title":["Human &amp; Experimental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09603271251409541","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/09603271251409541","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09603271251409541","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:49:36Z","timestamp":1777448976000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/09603271251409541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":38,"alternative-id":["10.1177\/09603271251409541"],"URL":"https:\/\/doi.org\/10.1177\/09603271251409541","relation":{},"ISSN":["0960-3271","1477-0903"],"issn-type":[{"value":"0960-3271","type":"print"},{"value":"1477-0903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"article-number":"09603271251409541"}}