Induced growth inhibition, cell cycle arrest and apoptosis in CD133+/CD44+ prostate cancer stem cells by flavopiridol

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dc.contributor.authorSoner, Burak Cem
dc.contributor.authorAktug, Huseyin
dc.contributor.authorAcikgoz, Eda
dc.contributor.authorDuzagac, Fahriye
dc.contributor.authorGuven, Ummu
dc.contributor.authorAyla, Sule
dc.contributor.authorCal, Cag
dc.date.accessioned2024-02-23T14:35:26Z
dc.date.available2024-02-23T14:35:26Z
dc.date.issued2014
dc.departmentNEÜen_US
dc.description.abstractFlavopiridol is a flavone that inhibits several cyclin-dependent kinases and exhibits potent growth-inhibitory activity, apoptosis and G(1)-phase arrest in a number of human tumor cell lines. Flavopiridol is currently undergoing investigation in human clinical trials. The present study focused on the effect of flavopiridol in cell proliferation, cell cycle progression and apoptosis in prostate cancer stem cells (CSCs). Therefore, cluster of differentiation 133 (CD133)(+high)/CD44(+high) prostate CSCs were isolated from the DU145 human prostate cancer cell line. The cells were treated with flavopiridol in a dose- and time-dependent manner to determine the inhibitory effect. Cell viability and proliferation were analyzed and the efficiency of flavopiridol was assessed using the sphere-forming assay. Flavopiridol was applied to monolayer cultures of CD133(high)/CD44(high) human prostate CSCs at the following final concentrations: 100, 300, 500 and 1000 nM. The cultures were incubated for 24, 48 and 72 h. The half maximal inhibitory concentration (IC50) value of the drug was determined as 500 nM for monolayer cells. Dead cells were analyzed prior and subsequent to exposure to increasing flavopiridol doses. Annexin-V and immunofluorescence analyses were performed for the evaluation of apoptotic pathways. According to the results, flavopiridol treatment caused significant growth inhibition at 500 and 1000 nM when compared to the control at 24 h. G(0)/G(1), analysis showed a statistically significant difference between 100 and 500 nM (P<0.005), 100 and 1000 nM (P<0.001), 300 and 1000 nM (P<0.001), and 500 and 1000 nM (P<0.001). Flavopiridol also significantly influenced the cells in the G(2)/M phase, particularly at highldose treatments. Flavopiridol induced growth inhibition and apoptosis at the IC50 dose (500 nM), resulting in a significant increase in immunofluorescence staining of caspase-3, caspase-8 and p53. In conclusion, the present results indicated that flavopiridol could be a useful therapeutic agent for prostate CSCs by inhibiting tumor growth and malignant progression, and inducing apoptosis.en_US
dc.identifier.doi10.3892/ijmm.2014.1930
dc.identifier.endpage1256en_US
dc.identifier.issn1107-3756
dc.identifier.issn1791-244X
dc.identifier.issue5en_US
dc.identifier.pmid25216351en_US
dc.identifier.scopus2-s2.0-84907189766en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage1249en_US
dc.identifier.urihttps://doi.org/10.3892/ijmm.2014.1930
dc.identifier.urihttps://hdl.handle.net/20.500.12452/16029
dc.identifier.volume34en_US
dc.identifier.wosWOS:000344423800008en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpandidos Publ Ltden_US
dc.relation.ispartofInternational Journal Of Molecular Medicineen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectFlavopiridolen_US
dc.subjectProstate Canceren_US
dc.subjectApoptosisen_US
dc.subjectStem Cellen_US
dc.titleInduced growth inhibition, cell cycle arrest and apoptosis in CD133+/CD44+ prostate cancer stem cells by flavopiridolen_US
dc.typeArticleen_US

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