Comparison of cell cycle components, apoptosis and cytoskeleton-related molecules and therapeutic effects of flavopiridol and geldanamycin on the mouse fibroblast, lung cancer and embryonic stem cells

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dc.contributor.authorAktug, Huseyin
dc.contributor.authorAcikgoz, Eda
dc.contributor.authorUysal, Aysegul
dc.contributor.authorOltulu, Fatih
dc.contributor.authorOktem, Gulperi
dc.contributor.authorYigitturk, Gurkan
dc.contributor.authorDemir, Kenan
dc.contributor.authorYavasoglu, Altug
dc.contributor.authorCetintas, Vildan Bozok
dc.date.accessioned2019-10-27T23:08:47Z
dc.date.available2019-10-27T23:08:47Z
dc.date.issued2016
dc.departmentEge Üniversitesien_US
dc.description.abstractSimilarities and differences in the cell cycle components, apoptosis and cytoskeleton-related molecules among mouse skin fibroblast cells (MSFs), mouse squamous cell lung carcinomas (SqCLCs) and mouse embryonic stem cells (mESCs) are important determinants of the behaviour and differentiation capacity of these cells. To reveal apoptotic pathways and to examine the distribution and the role of cell cycle-cell skeleton comparatively would necessitate tumour biology and stem cell biology to be assessed together in terms of oncogenesis and embryogenesis. The primary objectives of this study are to investigate the effects of flavopiridol, a cell cycle inhibitor, and geldanamycin, a heat shock protein inhibitor on mouse somatic, tumour and embryonic stem cells, by specifically focusing on alterations in cytoskeletal proteins, cell polarity and motility as well as cell cycle regulators. To meet these objectives, expression of several genes, cell cycle analysis and immunofluorescence staining of intracellular cytoskeletal molecules were performed in untreated and flavopiridol- or geldanamycin-treated cell lines. Cytotoxicity assays showed that SqCLCs are more sensitive to flavopiridol than MSFs and mESCs. Keratin-9 and keratin-2 expressions increased dramatically whereas cell cycle regulatory genes decreased significantly in the flavopiridol-treated MSFs. Flavopiridol-treated SqCLCs displayed a slight increase in several cell cytoskeleton regulatory genes as well as cell cycle regulatory genes. However, gene expression profiles of mESCs were not affected after flavopiridol treatment except the Cdc2a. Cytotoxic concentrations of geldanamycin were close to each other for all cell lines. Cdkn1a was the most increased gene in the geldanamycin-treated MSFs. However, expression levels of cell cytoskeleton-associated genes were increased dramatically in the geldanamycin-treated SqCLCs. Our results revealing differences in molecular mechanisms between embryogenesis and carcinogenesis may prove crucial in developing novel therapeutics that specifically target cancer cells.en_US
dc.description.sponsorshipEge UniversityEge University [BAP-2013-TIP-086]en_US
dc.description.sponsorshipThis study was supported by the Ege University Research Fund [grant number BAP-2013-TIP-086 (to H.A.)]. The authors wish to thank Ass. Prof. Dr. Umit A. Kayisli and Prof. Dr. Frederick Schatz (from the Department of Obstetrics and Gynecology, Ohio State University College of Medicine) for proofreading and major contributions to the manuscript.en_US
dc.identifier.doi10.1007/s13277-016-5108-9en_US
dc.identifier.endpage12440en_US
dc.identifier.issn1010-4283
dc.identifier.issn1423-0380
dc.identifier.issue9en_US
dc.identifier.pmid27324070en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage12423en_US
dc.identifier.urihttps://doi.org/10.1007/s13277-016-5108-9
dc.identifier.urihttps://hdl.handle.net/11454/52370
dc.identifier.volume37en_US
dc.identifier.wosWOS:000387075400083en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSage Publications Ltden_US
dc.relation.ispartofTumor Biologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectMouse skin fibroblast cellsen_US
dc.subjectMouse squamous cell lung carcinomasen_US
dc.subjectMouse embryonic stem cellen_US
dc.subjectCell cytoskeletonen_US
dc.subjectCell cycleen_US
dc.subjectCell cycle inhibitoren_US
dc.subjectFlavopiridolen_US
dc.subjectHeat shock protein inhibitoren_US
dc.subjectGeldanamycinen_US
dc.titleComparison of cell cycle components, apoptosis and cytoskeleton-related molecules and therapeutic effects of flavopiridol and geldanamycin on the mouse fibroblast, lung cancer and embryonic stem cellsen_US
dc.typeArticleen_US

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