Multifaceted actions of 8-amino-adenosine kill BCR–ABL positive cells
| العنوان: | Multifaceted actions of 8-amino-adenosine kill BCR–ABL positive cells |
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| المؤلفون: | Varsha Gandhi, Michael J. Keating, Rathi N. Pillai, Lisa S. Chen, Michael W. Thomas, Mary Ayres, Billie Nowak, Elizabeth J. Shpall |
| المصدر: | Leukemia & Lymphoma. 53:2024-2032 |
| بيانات النشر: | Informa UK Limited, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Cancer Research, Adenosine, Transcription, Genetic, Cell Survival, Poly ADP ribose polymerase, Fusion Proteins, bcr-abl, Antineoplastic Agents, Apoptosis, Biology, Piperazines, Article, chemistry.chemical_compound, Adenosine Triphosphate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, medicine, Humans, Protein Kinase Inhibitors, neoplasms, Cell Proliferation, ABL, Gene Expression Regulation, Leukemic, Kinase, Imatinib, Hematology, medicine.disease, Molecular biology, Pyrimidines, Oncology, chemistry, Drug Resistance, Neoplasm, Benzamides, Imatinib Mesylate, K562 Cells, Adenosine triphosphate, Chronic myelogenous leukemia, medicine.drug, K562 cells |
| الوصف: | Survival of chronic myelogenous leukemia (CML) cells is dependent on BCR-ABL kinase, the activity of which is contingent on the level of BCR-ABL protein and the availability of adenosine triphosphate (ATP). We hypothesized that 8-amino-adenosine (8-amino-Ado)-mediated reduction in cellular ATP level and inhibition of mRNA synthesis leading to a decrease in protein level would result in a multifaceted targeting of BCR-ABL. Using K562 cells, we demonstrated that there was a dose- and time-dependent increase in 8-amino-ATP accompanied by a 95% decline in the endogenous ATP pool. In parallel, 8-amino-Ado inhibited RNA synthesis and resulted in a depletion of BCR-ABL transcript. Consistent with this, BCR-ABL and ABL protein levels were also decreased. These effects were associated with the initiation of cell death as visualized by poly(ADP-ribose) polymerase (PARP) cleavage, decreased clonogenicity and greater than additive interaction with imatinib. In imatinib-sensitive and -resistant KBM5 cells, 8-amino-Ado treatment augmented the imatinib effect on growth inhibition. |
| تدمد: | 1029-2403 1042-8194 |
| DOI: | 10.3109/10428194.2012.678003 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d82be54971c620c5572ed4001e26ec1e https://doi.org/10.3109/10428194.2012.678003 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d82be54971c620c5572ed4001e26ec1e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10292403 10428194 |
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| DOI: | 10.3109/10428194.2012.678003 |