Synergistic effect of ponatinib and epigallocatechin-3-gallate induces apoptosis in chronic myeloid leukemia cells through altering expressions of cell cycle regulatory genes

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dc.contributor.authorGoker B.
dc.contributor.authorCaliskan C.
dc.contributor.authorCaglar H.O.
dc.contributor.authorKayabasi C.
dc.contributor.authorBalci T.
dc.contributor.authorTepedelen B.E.
dc.contributor.authorAygunes D.
dc.contributor.authorSusluer S.Y.
dc.contributor.authorMutlu Z.
dc.contributor.authorGunell N.S.
dc.contributor.authorKorkmaz M.
dc.contributor.authorSaydam G.
dc.contributor.authorGunduz C.
dc.contributor.authorAvci C.B.
dc.date.accessioned2024-07-22T08:15:14Z
dc.date.available2024-07-22T08:15:14Z
dc.date.issued2014
dc.description.abstractPurpose: Ponatinib (P) has been used for the treatment of chronic myeloid leukemia (CML) and it is known that inhibition of BCR-ABL fusion protein by ponatinib induces apoptosis of CML cells. Epigallocatechin-3-gallate (EGCG), which is a polyphenol in green tea, induces apoptosis in different types of cancer cells. The purpose of this study was to determine the cytotoxic and apoptotic effects of ponatinib and EGCG combination in K562 CML cell line. This study also aimed to detect alterations of the expression levels of cell cycle-regulation related genes after ponatinib and EGCG combination in K562 CML cell line. Methods: The cytotoxic effects of the compounds on K562 cells were determined in a time- and dose-dependent manner by using WST-1 analysis. The combination index (CI) isobologram was used to analyze the data. Apoptotic effects of P-EGCG were defined by flow cytometry and gene expressions were detected by RT-qPCR. Results: IC50 values of ponatinib and EGCG were 87.13 nM and 50μM, respectively. CI value of the P-EGCG was 0.658 and the combination showed synergistic effect (ED90 value: 28.39 nM ponatinib, 117.12 μg/ml EGCG). Ponatinib, EGCG and P-EGCG induced apoptosis compared to control cells. CyclinDl and CDC25A were downregulated by P-EGCG by 2.49 and 2.63-fold, respectively. TGF-β2 was upregulated by 4.57-fold. Conclusion: EGCG possesses cytotoxic and apoptotic properties and may cooperate with the growth inhibiting activity of ponatinib synergistically against CML cells. P-EGCG mediated apoptosis might be associated with upregulation of TGF-β2 gene and downregulation of cyclinDl and CDC25A genes.
dc.identifier.issn11070625
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/16705
dc.language.isoEnglish
dc.publisherZerbinis Publications
dc.subjectAntineoplastic Agents
dc.subjectApoptosis
dc.subjectCatechin
dc.subjectCell Cycle
dc.subjectFusion Proteins, bcr-abl
dc.subjectGene Expression
dc.subjectHumans
dc.subjectImidazoles
dc.subjectK562 Cells
dc.subjectLeukemia, Myelogenous, Chronic, BCR-ABL Positive
dc.subjectPyridazines
dc.subjectbeta glucuronidase
dc.subjectepigallocatechin gallate
dc.subjecthypoxanthine phosphoribosyltransferase
dc.subjectpolyphenol
dc.subjectponatinib
dc.subjectRNA 18S
dc.subjectantineoplastic agent
dc.subjectBCR ABL protein
dc.subjectcatechin
dc.subjectepigallocatechin gallate
dc.subjectimidazole derivative
dc.subjectponatinib
dc.subjectpyridazine derivative
dc.subjectantineoplastic activity
dc.subjectapoptosis
dc.subjectArticle
dc.subjectcell culture
dc.subjectcell cycle
dc.subjectcell cycle regulation
dc.subjectchronic myeloid leukemia
dc.subjectcontrolled study
dc.subjectcytotoxicity
dc.subjectflow cytometry
dc.subjectgene expression
dc.subjectgrowth inhibition
dc.subjecthuman
dc.subjecthuman cell
dc.subjectIC50
dc.subjectK562 cell line
dc.subjectregulator gene
dc.subjectreverse transcription
dc.subjectreverse transcription polymerase chain reaction
dc.subjectRNA isolation
dc.subjecttea
dc.subjectanalogs and derivatives
dc.subjectchronic myeloid leukemia
dc.subjectdrug effect
dc.subjectgenetics
dc.subjectK-562 cell line
dc.titleSynergistic effect of ponatinib and epigallocatechin-3-gallate induces apoptosis in chronic myeloid leukemia cells through altering expressions of cell cycle regulatory genes
dc.typeArticle

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