Combination of AT-101/cisplatin overcomes chemoresistance by inducing apoptosis and modulating epigenetics in human ovarian cancer cells

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dc.contributor.authorKaraca B.
dc.contributor.authorAtmaca H.
dc.contributor.authorBozkurt E.
dc.contributor.authorKisim A.
dc.contributor.authorUzunoglu S.
dc.contributor.authorKarabulut B.
dc.contributor.authorSezgin C.
dc.contributor.authorSanli U.A.
dc.contributor.authorUslu R.
dc.date.accessioned2024-07-22T08:18:33Z
dc.date.available2024-07-22T08:18:33Z
dc.date.issued2013
dc.description.abstractWe investigated the effects of AT-101/cisplatin combination treatment on the expression levels of apoptotic proteins and epigenetic events such as DNA methyltransferase (DNMT) and histone deacetylase (HDAC) enzyme activities in OVCAR-3 and MDAH-2774 ovarian cancer cells. XTT cell viability assay was used to evaluate cytotoxicity. For showing apoptosis, both DNA Fragmentation and caspase 3/7 activity measurements were performed. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. DNMT and HDAC activities were evaluated by ELISA assay and mRNA levels of DNMT1 and HDAC1 genes were quantified by qRT-PCR. Combination of AT-101/cisplatin resulted in strong synergistic cytotoxicity and apoptosis in human ovarian cancer cells. Combination treatment reduced some pivotal anti-apoptotic proteins such as Bcl-2, HIF-1A, cIAP-1, XIAP in OVCAR-3 cells, whereas p21, Bcl-2, cIAP-1, HSP27, Clusterin and XIAP in MDAH-2774 cells. Among the pro-apoptotic proteins, Bad, Bax, Fas, phospho-p53 (S46), Cleaved caspase-3, SMAC/Diablo, TNFR1 and Cytochrome c were induced in OVCAR-3 cells, whereas, Bax, TRAILR2, FADD, p27, phospho-p53 (S46), Cleaved caspase-3, Cytochrome c, SMAC/Diablo and TNFR1 were induced in MDAH-2774 cells. Combination treatment also inhibited both DNMT and HDAC activities and also mRNA levels in both ovarian cancer cells. AT-101 exhibits great potential in sensitization of human ovarian cancer cells to cisplatin treatment in vitro, suggesting that the combination of AT-101 with cisplatin may hold great promise for development as a novel chemotherapeutic approach to overcome platinum-resistance in human ovarian cancer. © 2012 Springer Science+Business Media Dordrecht.
dc.identifier.DOI-ID10.1007/s11033-012-2469-z
dc.identifier.issn15734978
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/17354
dc.language.isoEnglish
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectApoptosis
dc.subjectCaspase 3
dc.subjectCaspase 7
dc.subjectCell Line, Tumor
dc.subjectCell Survival
dc.subjectCisplatin
dc.subjectDNA (Cytosine-5-)-Methyltransferase
dc.subjectDNA Fragmentation
dc.subjectDNA Methylation
dc.subjectDose-Response Relationship, Drug
dc.subjectDrug Resistance, Neoplasm
dc.subjectDrug Synergism
dc.subjectEpigenesis, Genetic
dc.subjectFemale
dc.subjectFluorescent Antibody Technique
dc.subjectGossypol
dc.subjectHistone Deacetylases
dc.subjectHumans
dc.subjectOvarian Neoplasms
dc.subjectcaspase 3
dc.subjectcaspase 7
dc.subjectcell DNA
dc.subjectcisplatin
dc.subjectclusterin
dc.subjectcytochrome c
dc.subjectdeath receptor 5
dc.subjectDNA methyltransferase 1
dc.subjectFas antigen
dc.subjectFas associated death domain protein
dc.subjectheat shock protein 27
dc.subjecthistone deacetylase 1
dc.subjecthypoxia inducible factor 1alpha
dc.subjectinhibitor of apoptosis protein 1
dc.subjectisosorbide
dc.subjectmessenger RNA
dc.subjectprotein BAD
dc.subjectprotein Bax
dc.subjectprotein bcl 2
dc.subjectprotein p21
dc.subjectprotein p27
dc.subjectprotein p53
dc.subjectsecond mitochondrial activator of caspase
dc.subjecttumor necrosis factor receptor 1
dc.subjectX linked inhibitor of apoptosis
dc.subjectapoptosis
dc.subjectarticle
dc.subjectcancer cell
dc.subjectcancer resistance
dc.subjectcell strain
dc.subjectcell strain MDAH 2774
dc.subjectcell strain OVCAR 3
dc.subjectcell viability
dc.subjectchemosensitization
dc.subjectcontrolled study
dc.subjectDNA fragmentation
dc.subjectDNMT1 gene
dc.subjectdrug cytotoxicity
dc.subjectdrug potentiation
dc.subjectenzyme activity
dc.subjectenzyme inhibition
dc.subjectepigenetics
dc.subjectHDAC1 gene
dc.subjecthuman
dc.subjecthuman cell
dc.subjectin vitro study
dc.subjectovary cancer
dc.subjectprotein cleavage
dc.subjectprotein expression
dc.titleCombination of AT-101/cisplatin overcomes chemoresistance by inducing apoptosis and modulating epigenetics in human ovarian cancer cells
dc.typeArticle

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