{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T23:17:56Z","timestamp":1781651876696,"version":"3.54.5"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Sorafenib (SOR) is an orally administered molecular targeted agent in the systemic chemotherapy of hepatocellular carcinoma (HCC). However, the partial response of SOR is limited due to its adverse side effect and high heterogeneity and resistant phenotype of HCC. In the current study, we investigated synergistic effects of SOR and usnic acid (UA) on HCC cell lines including HepG2 and SNU-449, and a normal cell line, HUVEC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The antiproliferative and apoptotic effects of combination therapy and SOR alone were analysed by WST-1 and Annexin V analysis, respectively. Furthermore, cell cycle, gene expression analysis of SOR-targeted kinases and acridine orange\u2013ethidium bromide staining were also performed in combined treatments.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Our results demonstrated that SOR and UA combination indicated a strong synergism in HCC cell lines and reduced SOR toxicity in HUVEC cells. Additionally, the combination treatment SOR and UA significantly induced much more apoptotic cell death and G0\/G1 arrest through downregulation of SOR-targeted kinases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Consequently, SOR and UA combination could be a new therapeutic strategy for HCC treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jphp.13097","type":"journal-article","created":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T02:33:13Z","timestamp":1556245993000},"page":"1119-1132","source":"Crossref","is-referenced-by-count":16,"title":["Investigation of new treatment option for hepatocellular carcinoma: a combination of sorafenib with usnic acid"],"prefix":"10.1093","volume":"71","author":[{"given":"Beste","family":"Yurdacan","sequence":"first","affiliation":[{"name":"Pharmacology Department, Faculty of Pharmacy, Ege University , Izmir,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unal","family":"Egeli","sequence":"additional","affiliation":[{"name":"Medical Biology Department, Faculty of Medicine, Bursa Uludag University , Bursa,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2088-9914","authenticated-orcid":false,"given":"Gamze","family":"Guney Eskiler","sequence":"additional","affiliation":[{"name":"Medical Biology Department, Faculty of Medicine, Sakarya University , Sakarya,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isil Ezgi","family":"Eryilmaz","sequence":"additional","affiliation":[{"name":"Medical Biology Department, Faculty of Medicine, Bursa Uludag University , Bursa,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulsah","family":"Cecener","sequence":"additional","affiliation":[{"name":"Medical Biology Department, Faculty of Medicine, Bursa Uludag University , Bursa,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berrin","family":"Tunca","sequence":"additional","affiliation":[{"name":"Medical Biology Department, Faculty of Medicine, Bursa Uludag University , Bursa,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"2024103012340571400_jphp13097-cit-0001","doi-asserted-by":"crossref","first-page":"S516","DOI":"10.1016\/S0168-8278(14)61439-2","article-title":"P1280 epidemiological trends of hepatocellular carcinoma in Austria","volume":"60","author":"Pinter","year":"2014","journal-title":"J Hepatol"},{"key":"2024103012340571400_jphp13097-cit-0002","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/ijc.1440","article-title":"Estimating the world cancer burden: Globocan 2000","volume":"94","author":"Maxwell 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