Radotinib Induces Apoptosis of CD11b+ Cells Differentiated from Acute Myeloid Leukemia Cells
| Autor: | SuJin Koh, Jae-Cheol Jo, Eui-Kyu Noh, Dong-Joon Yoon, Young Joo Min, Yunsuk Choi, Jin Ho Baek, Jae-Hoo Park, Hawk Kim, Sook-Kyoung Heo |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Myeloid Cellular differentiation Chemosensitizer lcsh:Medicine Antineoplastic Agents Apoptosis Tretinoin Biology Radotinib LYN hemic and lymphatic diseases Cell Line Tumor medicine Leukocytes Humans lcsh:Science neoplasms Protein Kinase Inhibitors Aged Aged 80 and over Multidisciplinary CD11b Antigen lcsh:R Myeloid leukemia Middle Aged medicine.disease Dasatinib Leukemia Leukemia Myeloid Acute medicine.anatomical_structure src-Family Kinases Pyrazines Benzamides Cancer research lcsh:Q Female medicine.drug Research Article |
| Zdroj: | PLoS ONE PLOS ONE(10): 6 PLoS ONE, Vol 10, Iss 6, p e0129853 (2015) |
| ISSN: | 1932-6203 |
| Popis: | Radotinib, developed as a BCR/ABL tyrosine kinase inhibitor (TKI), is approved for the second-line treatment of chronic myeloid leukemia (CML) in South Korea. However, therapeutic effects of radotinib in acute myeloid leukemia (AML) are unknown. In the present study, we demonstrate that radotinib significantly decreases the viability of AML cells in a dose-dependent manner. Kasumi-1 cells were more sensitive to radotinib than NB4, HL60, or THP-1 cell lines. Furthermore, radotinib induced CD11b expression in NB4, THP-1, and Kasumi-1 cells either in presence or absence of all trans-retinoic acid (ATRA). We found that radotinib promoted differentiation and induced CD11b expression in AML cells by downregulating LYN. However, CD11b expression induced by ATRA in HL60 cells was decreased by radotinib through upregulation of LYN. Furthermore, radotinib mainly induced apoptosis of CD11b(+) cells in the total population of AML cells. Radotinib also increased apoptosis of CD11b(+) HL60 cells when they were differentiated by ATRA/dasatinib treatment. We show that radotinib induced apoptosis via caspase-3 activation and the loss of mitochondrial membrane potential (Delta psi(m)) in CD11b(+) cells differentiated from AML cells. Our results suggest that radotinib may be used as a candidate drug in AML or a chemosensitizer for treatment of AML by other therapeutics. |
| Databáze: | OpenAIRE |
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