Summary Purpose: Ponatinib (P) has been used for the treatment of chronic myeloid leukemia (CML) and it is known that in- hibition 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 ponati- nib and EGCG combination in K562 CML cell line. This study also aimed to detect alterations of the expression lev- els of cell cycle-regulation related genes aſter 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 man- ner 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 expres- sions 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). Ponati- nib, EGCG and P-EGCG induced apoptosis compared to control cells. CyclinD1 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 up- regulation of TGF-β2 gene and downregulation of cyclinD1 and CDC25A genes. Key words: chronic myeloid leukemia, epigallocatechin-3-gal- late, ponatinib, tyrosine kinase inhibitors Synergistic effect of ponatinib and epigallocatechin-3-gallate induces apoptosis in chronic myeloid leukemia cells through altering expressions of cell cycle regulatory genes Bakiye Goker1, Cansu Caliskan1, Hasan Onur Caglar2, Cagla Kayabasi1, Tugce Balci1, Burcu Erbaykent Tepedelen3, Duygu Aygunes1, Sunde Yilmaz Susluer1, Zeynep Mutlu1, Nur Selvi Gunel1, Mehmet Korkmaz4, Guray Saydam5, Cumhur Gunduz1, Cigir Biray Avci1 1Department of Medical Biology, School of Medicine, Ege University, Izmir; 2Ege University, Health Science Institute, Department of Stem Cell, Bornova, Izmir; 3Department of Molecular Biology and Genetics, Faculty of Science and Letters, Avrasya University, Trabzon; 4Celal Bayar University, Faculty of Medicine, Department of Medical Biology, Manisa; 5Department of Hematology, School of Medicine, Ege University, Izmir, Turkey Correspondence to: Cigir Biray Avci, PhD. Ege University Medical Faculty, Department of Medical Biology, Bornova, 35100, Izmir, Turkey. Cell phone: +90 532 654 55 50, Fax: +90 232 3420542, E-mail: cbavci@gmail.com Received: 27/03/2014; Accepted: 23/04/2014 Introduction CML is a malignant myeloproliferative disor- der of adults, originating from hematopoietic stem cells (HSCs), and the median age on presentation is approximately 60 years [1-3]. Because CML is a clonal disorder of HSCs, not only myeloid cells but also other hematopoietic cells in peripheral blood are affected by this condition [1]. Patients with CML are generally diagnosed by the pres- ence of Philadelphia chromosome [4,5]. This chro- mosome is the result of translocation between chromosome 22 (BCR gene), and chromosome 9 (ABL gene) [6,7]. BCR-ABL fusion protein which has abnormal tyrosine kinase activity results by this reciprocal translocation [8]. BCR-ABL fusion protein can activate different signal pathways such as MAP kinase, PI3 kinase, and Jak-Stat pathways which are associated with cell proliferation and malignant transformation [9]. BCR-ABL induces uncontrolled G1-S phase transition of the cell cycle and reduces the activ- JBUON 2014; 19(4): 992-998 ISSN: 1107-0625, online ISSN: 2241-6293 • www.jbuon.com E-mail: editorial_office@jbuon.com ORIGINAL ARTICLE