Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/4989
Title: Roles of ceramide synthase and ceramide clearence genes in nilotinib-induced cell death in chronic myeloidleukemia cells
Authors: Camgöz, Aylin
Gençer, Emel Başak
Ural, Ali Uğur
Avcu, Ferit
Baran, Yusuf
Keywords: Chronic myeloid leukemia
Apoptosis
Bioactive sphingolipids
Ceramides
Nilotinib
Publisher: Informa Healthcare
Source: Camgöz, A., Gençer, E.B., Ural, A.U., Avcu, F., and Baran, Y. (2011). Roles of ceramide synthase and ceramide clearence genes in nilotinib-induced cell death in chronic myeloidleukemia cells. Leukemia and Lymphoma, 52(8), 1574-1584. doi:10.3109/10428194.2011.568653
Abstract: In this study, we aimed to increase the sensitivity of human K562 and Meg-01 chronic myeloid leukemia (CML) cells to nilotinib by targeting bioactive sphingolipids, in addition to investigating the roles of ceramide metabolizing genes in nilotinib induced apoptosis. Cytotoxic effects of nilotinib, C8:ceramide, glucosyle ceramide synthase (GCS) and sphingosine kinase-1 (SK-1) inhibitors were determined by XTT cell proliferation assay and synergism between the agents was determined by isobologram analysis. Also, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) results demonstrated that expression levels of longevity assurance (LASS) genes in response to nilotinib were correlated with sensitivity to nilotinib. For the first time, The results of this study showed for the first time that nilotinib induces apoptosis through upregulating ceramide synthase genes and downregulating SK-1 in CML cells in addition to inhibition of BCR/ABL. On the other hand, manipulating bioactive sphingolipids toward generation/accumulation of ceramides increased the apoptotic effects of nilotinib in CML cells.
URI: http://doi.org/10.3109/10428194.2011.568653
http://hdl.handle.net/11147/4989
ISSN: 1042-8194
1042-8194
1029-2403
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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