Effective and new potent drug combination: histone deacetylase and Wnt/beta-catenin pathway inhibitors in lung carcinoma cells

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dc.authoridMerve Erkısa Genel / 0000-0002-3127-742X
dc.authorscopusidMerve Erkısa Genel / 57126208900
dc.authorwosidMerve Erkısa Genel / FZJ-0775-2022
dc.contributor.authorAkgün, Oğuzhan
dc.contributor.authorErkısa Genel, Merve
dc.contributor.authorArı, Ferda
dc.date.accessioned2020-08-30T20:06:38Z
dc.date.available2020-08-30T20:06:38Z
dc.date.issued2019
dc.departmentİstinye Üniversitesi, Rektörlüken_US
dc.description.abstractLung 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 investigated on human lung cancer cell line. The effects of the compounds alone and combination therapy on cell viability were determined by sulforhodamine B and adenosine 5 '-triphosphate 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 species (ROS) level in combination therapy was determined by H2DCFDA staining. The effect of N-acetyl-l-cysteine 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-time 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. When 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.en_US
dc.description.sponsorshipResearch Fund of Bursa Uludag University [OUAP (F)-2015/15]en_US
dc.description.sponsorshipResearch Fund of Bursa Uludag University, Grant/Award Number: OUAP (F)-2015/15en_US
dc.identifier.citationAkgun, O., Erkisa, M., & Ari, F. (2019). Effective and new potent drug combination: Histone deacetylase and Wnt/β‐catenin pathway inhibitors in lung carcinoma cells. Journal of cellular biochemistry, 120(9), 15467-15482.en_US
dc.identifier.doi10.1002/jcb.28813en_US
dc.identifier.endpage15482en_US
dc.identifier.issn0730-2312en_US
dc.identifier.issn1097-4644en_US
dc.identifier.issue9en_US
dc.identifier.pmid31037769en_US
dc.identifier.scopus2-s2.0-85069524183en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage15467en_US
dc.identifier.urihttps://doi.org/10.1002/jcb.28813
dc.identifier.urihttps://hdl.handle.net/20.500.12713/579
dc.identifier.volume120en_US
dc.identifier.wosWOS:000476804200119en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorErkısa Genel, Merveen_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofJournal of Cellular Biochemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectApoptosisen_US
dc.subjectLung Canceren_US
dc.subjectNiclosamideen_US
dc.subjectValproic Aciden_US
dc.titleEffective and new potent drug combination: histone deacetylase and Wnt/beta-catenin pathway inhibitors in lung carcinoma cellsen_US
dc.typeArticleen_US

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