Effects of flavopiridol on critical regulation pathways of CD133(high)/CD44(high) lung cancer stem cells

dc.contributor.authorCetintas, Vildan Bozok
dc.contributor.authorAcikgoz, Eda
dc.contributor.authorYigitturk, Gurkan
dc.contributor.authorDemir, Kenan
dc.contributor.authorOktem, Gulperi
dc.contributor.authorKaymaz, Burcin Tezcanli
dc.contributor.authorOltulu, Fatih
dc.contributor.authorAktug, Huseyin
dc.date.accessioned2019-10-27T11:25:50Z
dc.date.available2019-10-27T11:25:50Z
dc.date.issued2016
dc.departmentEge Üniversitesien_US
dc.description.abstractBackground:Flavopiridol a semisynthetic flavone that inhibits cyclin-dependent kinases (CDKs) and has growth-inhibitory activity and induces a blockade of cell-cycle progression at G1-phase and apoptosis in numerous human tumor cell lines and is currently under investigation in phase II clinical trials. Cancer stem cells (CSCs) are comprised of subpopulation of cells in tumors that have been proposed to be responsible for recurrence and resistance to chemotherapy. The aim of the present study was to investigate the effects of flavopiridol in cancer stem cell cytoskeleton, cell adhesion, and epithelial to mesenchymal transition in CSCs.Methods:The cells were treated with flavopiridol to determine the inhibitory effect. Cell viability and proliferation were determined by using the WST-1 assay. Caspase activity and immunofluorescence analyses were performed for the evaluation of apoptosis, cell cytoskeleton, and epithelial-mesenchymal transition (EMT) markers. The effects of flavopiridol on the cell cycle were also evaluated. Flow cytometric analysis was used to detect the percentages of CSCs subpopulation. We analyzed the gene expression patterns to predict cell cycle and cell cytoskeleton in CSCs by RT-PCR.Results:Flavopiridol-induced cytotoxicity and apoptosis at the IC50 dose, resulting in a significant increase expression of caspases activity. Cell cycle analyses revealed that flavopiridol induces G1 phase cell cycle arrest. Flavopiridol significantly decreased the mRNA expressions of the genes that regulate the cell cytoskeleton and cell cycle components and cell motility in CSCs.Conclusion:Our results suggest that Flavopiridol has activity against lung CSCs and may be effective chemotherapeutic molecule for lung cancer treatment.en_US
dc.identifier.doi10.1097/MD.0000000000005150
dc.identifier.issn0025-7974
dc.identifier.issn1536-5964
dc.identifier.issn0025-7974en_US
dc.identifier.issn1536-5964en_US
dc.identifier.issue43en_US
dc.identifier.urihttps://doi.org/10.1097/MD.0000000000005150
dc.identifier.urihttps://hdl.handle.net/11454/33434
dc.identifier.volume95en_US
dc.identifier.wosWOS:000387272700018en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.language.isoenen_US
dc.publisherLippincott Williams & Wilkinsen_US
dc.relation.ispartofMedicineen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectapoptosisen_US
dc.subjectcell cytoskeletonen_US
dc.subjectEMTen_US
dc.subjectflavopiridolen_US
dc.subjectlung canceren_US
dc.subjectstem cellen_US
dc.titleEffects of flavopiridol on critical regulation pathways of CD133(high)/CD44(high) lung cancer stem cellsen_US
dc.typeArticleen_US

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