Show simple item record

dc.contributor.authorObakan, Pınar
dc.contributor.authorAlkurt, Gizem
dc.contributor.authorKöse, Betsi
dc.contributor.authorÇoker Gürkan, Ajda
dc.contributor.authorArısan, Elif Damla
dc.contributor.authorCoşkun, Deniz
dc.contributor.authorPalavan Unsal, Narçin
dc.date.accessioned2018-07-16T08:45:39Z
dc.date.available2018-07-16T08:45:39Z
dc.date.issued2014
dc.identifier.issn1300-0152
dc.identifier.urihttps://doi.org/10.3906/biy-1405-87
dc.identifier.urihttps://hdl.handle.net/11413/2103
dc.description.abstractRoscovitine and purvalanol are specific cyclin-dependent kinase (CDK) inhibitors, which induce apoptosis by triggering cell cycle arrest in various cancer cells such as colon, prostate, and breast cancer cells. Although the apoptotic action of roscovitine was clarified at the molecular level, the exact mechanism of purvalanol-induced apoptosis is still under investigation. The mitogen-activated protein kinase (MAPK) signaling cascade is activated by different inducers related to growth, proliferation, differentiation processes, or environmental stress factors. Recent reports showed that modulation of MAPKs might lead to regulation of c-Myc, which is a transcription factor for the polyamine (PA) biosynthesis enzyme, ornithine decarboxylase (ODC). PAs are amine-derived cationic molecules that play crucial roles in cell proliferation, growth, and differentiation. In this study, we investigated the potential role of the MAPK signaling cascade in the purvalanol-induced apoptosis mechanism by comparing the results of roscovitine in MCF7 and MDA-MB-231 breast cancer cells. We found that CDK inhibitors decreased the cell viability in a dose-and time-dependent manner in MCF-7 and MDA-MB-231 cancer cells. Although both CDK inhibitors induced cell cycle arrest, which led to apoptosis by activating caspases and PARP cleavage in MCF-7 breast cancer cells, the apoptotic effect of purvalanol was less than that of roscovitine in MDA-MB-231 cells. Inhibition of MAPKs prevented CDK inhibitor-induced cell viability loss in both cell lines. We determined that purvalanol downregulated c-Myc and ODC expression levels, which led to sharp decrease in the PA pool in MCF-7 cells. On the contrary, purvalanol did not significantly alter c-Myc expression levels, which led to de novo biosynthesis of ODC in a time-dependent manner in MDA-MB-231 cells. Therefore, we suggest that a purvalanol-mediated resistance phenotype might be a possible outcome of c-Myc-mediated ODC expression level in MDA-MB-231 cells.tr_TR
dc.language.isoen_UStr_TR
dc.publisherTubitak Scientific & Technical Research Council Turkey, Ataturk Bulvarı No 221, Kavaklıdere, Ankara, 00000, Turkeytr_TR
dc.relationTurkish Journal of Biologytr_TR
dc.subjectBreast cancertr_TR
dc.subjectcyclin-dependent kinase inhibitorstr_TR
dc.subjectpurvalanoltr_TR
dc.subjectmitogen-activated protein kinasestr_TR
dc.subjectpolyaminestr_TR
dc.subjectapoptosistr_TR
dc.subjectc-Myctr_TR
dc.subjectActivated Protein-Kinasetr_TR
dc.subjectRoscovitine-Induced Apoptosistr_TR
dc.subjectPolyamine Catabolic Pathwaytr_TR
dc.subjectCyclin-Dependent Kinasestr_TR
dc.subjectCdk Inhibitorstr_TR
dc.subjectArresttr_TR
dc.subjectDeathtr_TR
dc.subjectJnktr_TR
dc.subjectErktr_TR
dc.subjectGrowthtr_TR
dc.titleDownregulation of c-Myc mediated ODC expression after purvalanol treatment is under control of upstream MAPK signaling axis in MCF-7 breast cancer cellstr_TR
dc.typeArticletr_TR
dc.contributor.authorID156421tr_TR
dc.contributor.authorID125860tr_TR
dc.contributor.authorID113920tr_TR
dc.contributor.authorID6125tr_TR


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record