Academic Journal
Targeting c-KIT (CD117) by dasatinib and radotinib promotes acute myeloid leukemia cell death
| العنوان: | Targeting c-KIT (CD117) by dasatinib and radotinib promotes acute myeloid leukemia cell death |
|---|---|
| المؤلفون: | Heo, Sook-Kyoung, Noh, Eui-Kyu, Kim, Jeong Yi, Jeong, Yoo Kyung, Jo, Jae-Cheol, Choi, Yunsuk, Koh, SuJin, Baek, Jin Ho, Min, Young Joo, Kim, Hawk |
| المصدر: | Scientific Reports ; volume 7, issue 1 ; ISSN 2045-2322 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2017 |
| الوصف: | Dasatinib and radotinib are oral BCR-ABL tyrosine kinase inhibitors that were developed as drugs for the treatment of chronic myeloid leukemia. We report here that the c-KIT (CD117) targeting with dasatinib and radotinib promotes acute myeloid leukemia (AML) cell death, and c-KIT endocytosis is essential for triggering c-KIT-positive AML cell death by dasatinib and radotinib during the early stages. In addition, dasatinib and radotinib reduce heat shock protein 90β (HSP90β) expression and release Apaf-1 in c-KIT-positive AML cells. Finally, this activates a caspase-dependent apoptotic pathway in c-KIT-positive AML cells. Moreover, the inhibition of c-KIT endocytosis by dynamin inhibitor (DY) reversed cell viability and c-KIT expression by dasatinib and radotinib. HSP90β expression was recovered by DY in c-KIT-positive AML cells as well. Furthermore, the effect of radotinib on c-KIT and HSP90β showed the same pattern in a xenograft animal model using HEL92.1.7 cells. Therefore, dasatinib and radotinib promote AML cell death by targeting c-KIT. Taken together, these results indicate that dasatinib and radotinib treatment have a potential role in anti-leukemic therapy on c-KIT-positive AML cells. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41598-017-15492-5 |
| الاتاحة: | http://dx.doi.org/10.1038/s41598-017-15492-5 https://www.nature.com/articles/s41598-017-15492-5.pdf https://www.nature.com/articles/s41598-017-15492-5 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.FD946159 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-017-15492-5 |
|---|