Yurdacan, BesteEskiler, Gamze Güney2023-06-142023-06-142019-07Yurdacan, B. vd. (2019). ''Investigation of new treatment option for hepatocellular carcinoma: a combination of sorafenib with usnic acid''. Journal of Pharmacy and Pharmacology, 71(7), 1119-1132.0022-35732042-7158https://doi.org/10.1111/jphp.13097https://academic.oup.com/jpp/article/71/7/1119/6122173http://hdl.handle.net/11452/33037Objectives 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. Methods 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-ethidium bromide staining were also performed in combined treatments. Key findings 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. Conclusions Consequently, SOR and UA combination could be a new therapeutic strategy for HCC treatment.eninfo:eu-repo/semantics/openAccessCombination treatmentHepatocellular carcinomaSorafenibUsnic acidAntitumor-activityCancer-cellsInhibitionPathwayGeneP16Pharmacology & pharmacyAnnexin A5Antineoplastic AgentsApoptosisBenzofuransCarcinoma, HepatocellularCell Line, TumorCell ProliferationDrug SynergismDrug Therapy, CombinationHep G2 CellsHumansLiver NeoplasmsProtein-Tyrosine KinasesSorafenibArticle0004709774000102-s2.0-850650447971119113271731025377Pharmacology & pharmacyUsnic Acid; Extract; Lichen (Disease)Acridine orangeEthidium bromideLipocortin 5PhosphotransferaseSorafenibUsnic acidAntineoplastic agentBenzofuran derivativeProtein tyrosine kinaseAntiproliferative activityApoptosisArticleAutophagyCell cycle arrestCell organelleCell structureControlled studyDown regulationDrug cytotoxicityDrug potentiationGene expressionHep-G2 cell lineHepatocellular carcinoma cell lineHumanHuman cellHUVEC cell lineLiver cell carcinomaPercentage of cells in G0/G1 phaseProtein expressionCell proliferationCombination drug therapyDrug effectLiver cell carcinomaLiver tumorMetabolismPathologyTumor cell line