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dc.contributor.authorÇoker Gürkan, Ajda
dc.contributor.authorArısan, Elif Damla
dc.contributor.authorObakan Yerlikaya, Pınar
dc.contributor.authorİlhan, Halime
dc.contributor.authorÜnsal Palavan, Zeynep Narçın
dc.date.accessioned2018-07-24T08:58:40Z
dc.date.available2018-07-24T08:58:40Z
dc.date.issued2018-06
dc.identifier.issn2211-3428
dc.identifier.other2211-3436
dc.identifier.urihttps://doi.org/10.1007/s13402-017-0369-x
dc.identifier.urihttps://hdl.handle.net/11413/2294
dc.description.abstractOne of the recently developed polyamine (PA) analogues, N (1) ,N (11)-diethylnorspermine (DENSpm), has been found to act as an apoptotic inducer in melanoma, breast, prostate and colon cancer cells. Also, its potential to induce autophagy has been established. Unfolded protein responses and starvation of amino acids are known to trigger autophagy. As yet, however, the molecular mechanism underlying PA deficiency-induced autophagy is not fully clarified. Here, we aimed to determine the apoptotic effect of DENSpm after autophagy inhibition by 3-methyladenine (3-MA) or siRNA-mediated Beclin-1 silencing in colon cancer cells. The apoptotic effects of DENSpm after 3-MA treatment or Beclin-1 silencing were determined by PI and AnnexinV/PI staining in conjunction with flow cytometry. Intracellular PA levels were measured by HPLC, whereas autophagy and the expression profiles of PA key players were determined in HCT116, SW480 and HT29 colon cancer cells by Western blotting. We found that DENSpm-induced autophagy was inhibited by 3-MA treatment and Beclin-1 silencing, and that apoptotic cell death was increased by PA depletion and spermidine/spermine N (1)-acetyltransferase (SSAT) upregulation. We also found that autophagy inhibition led to DENSpm-induced apoptosis through Atg5 down-regulation, p62 degradation and LC3 lipidation in both HCT116 and SW480 cells. p53 deficiency did not alter the response of the colon cancer cells to DENSpm-induced apoptotic cell death under autophagy suppression conditions. From our results we conclude that DENSpm-induced apoptotic cell death is increased when autophagy is inhibited by 3-MA or Beclin-1 siRNA through PA depletion and PA catabolic activation in colon cancer cells, regardless p53 mutation status.tr_TR
dc.language.isoen_UStr_TR
dc.publisherSpringer, Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlandstr_TR
dc.relationCellular Oncologytr_TR
dc.subjectColon cancertr_TR
dc.subjectApoptosistr_TR
dc.subjectAutophagytr_TR
dc.subjectPolyamine analoguetr_TR
dc.subjectDENSpmtr_TR
dc.subjectHuman-Melanoma Cellstr_TR
dc.subjectPolyamine Analog N-1,N-11-Diethylnorsperminetr_TR
dc.subjectSpermidine/Spermine N-1-Acetyltransferasetr_TR
dc.subjectCarcinoma-Cellstr_TR
dc.subjectInductiontr_TR
dc.subjectResistancetr_TR
dc.subjectDeathtr_TR
dc.subjectMetabolismtr_TR
dc.subjectCatabolismtr_TR
dc.subjectModulatorstr_TR
dc.titleInhibition of autophagy enhances DENSpm-induced apoptosis in human colon cancer cells in a p53 independent mannertr_TR
dc.typeArticletr_TR
dc.contributor.authorID125860tr_TR
dc.contributor.authorID113920tr_TR
dc.contributor.authorID156421tr_TR
dc.contributor.authorID6125tr_TR
dc.identifier.wos432218500005
dc.identifier.wos432218500005en
dc.identifier.scopus2-s2.0-85042608353
dc.identifier.scopus2-s2.0-85042608353en
dc.identifier.pubmed29492901
dc.identifier.pubmed29492901en


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