{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:46:11Z","timestamp":1786977971256,"version":"build-2736575974"},"reference-count":67,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T00:00:00Z","timestamp":1556496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Research Fund of Bursa Uludag University","award":["OUAP(F)-2015\/15"],"award-info":[{"award-number":["OUAP(F)-2015\/15"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Lung cancer is the most commonly diagnosed cancer worldwide with a high mortality rate. In this study, the therapeutic effect of combination valproic acid and niclosamide was\u00a0investigated on human lung cancer cell line.\u00a0The effects of the compounds alone and combination therapy on cell viability were determined by sulforhodamine B and adenosine 5\u2032\u2010triphosphate viability assays. Flow cytometry was used to determine the cell death mechanism and DNA damage levels responsible for the cytotoxic effects of combination therapy. The presence of apoptosis in cells was supported by fluorescence microscopy and also by using inhibitors of the apoptotic signaling pathway. The increase in cellular reactive oxygen\u00a0species\u00a0(ROS) level in combination therapy was determined by H2DCFDA staining. The effect of N\u2010acetyl\u2010\n                    <jats:sc>l<\/jats:sc>\n                    \u2010cysteine combination on ROS increase was investigated on cell viability. In addition, the expression levels of the proteins associated with epigenetic regulation and cell death were analyzed by Western blotting and gene expression levels were determined using real\u2010time quantitative polymerase chain reaction.It was observed that the combination therapy showed a cytotoxic effect on the A549 lung cancer cells compared to the individual use of the inhibitors. The absence of this effect on normal lung cells revealed the presence of a selective toxic effect. When the mechanism of cytotoxicity is examined, it has been observed that combination therapy initiates the activation of tumor necrosis receptors and causes apoptosis by activated caspase. It was also observed that this extrinsic apoptotic pathway was activated on the mitochondrial pathway. In addition, ER stress and mitochondrial membrane potential loss associated with increased ROS levels induce cell death.\u00a0When the data in this study were evaluated, combination therapy caused a dramatic decrease in cell viability by inducing the extrinsic apoptotic pathway in lung cancer cell line. Therefore, it was concluded that it can be used as an effective and new treatment option for lung cancer.\n                  <\/jats:p>","DOI":"10.1002\/jcb.28813","type":"journal-article","created":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T22:11:23Z","timestamp":1556662283000},"page":"15467-15482","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Effective and new potent drug combination: Histone deacetylase and Wnt\/\u03b2\u2010catenin pathway inhibitors in lung carcinoma cells"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8410-1786","authenticated-orcid":false,"given":"Oguzhan","family":"Akgun","sequence":"first","affiliation":[{"name":"Department of Biology, Science and Art Faculty Bursa Uludag University Bursa 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