Academic Journal

Suberoylanilide hydroxamic acid (SAHA) and cladribine synergistically induce apoptosis in NK-LGL leukaemia

التفاصيل البيبلوغرافية
العنوان: Suberoylanilide hydroxamic acid (SAHA) and cladribine synergistically induce apoptosis in NK-LGL leukaemia
المؤلفون: Sun, Xiaoshen, Hasanali, Zainul S., Chen, Allshine, Zhang, Dianzheng, Liu, Zin, Wang, Hong Gang, Feith, David J., Loughran, Thomas P., Jr., Xu, Kailin
المصدر: PCOM Scholarly Papers
سنة النشر: 2014
المجموعة: Philadelphia College of Osteopathic Medicine: DigitalCommons@PCOM
مصطلحات موضوعية: Natural Killer Large Granular Lymphocyte Leukaemia, Vorinostat, Cladribine, histone deacetylation, Oncology
الوصف: Natural killer (NK) large granular lymphocyte (LGL) leukaemia features a clonal proliferation of CDNK cells that can be classified into either aggressive or chronic categories. The NKL cell line, derived from an aggressive Asian NK cell leukaemia, and patient samples from chronic NK LGLleukaemia were used in our study to probe for synergistic efficacy of the epigenetic drugs vorinostat (SAHA) and cladribine in this disease. We demonstrate that histone deacetylases (HDACs) are over-expressed in both aggressive and chronic NK leukaemia. Administration of the HDAC inhibitor SAHA reduces class I and II HDAC expression and enhances histone acetylation in leukaemic NK cells. In vitro combination treatment with SAHA and cladribine dose-dependently exerts synergistic cytotoxic and apoptotic effects on leukaemic NK cells. Expression profiling of apoptotic regulatory genes suggests that both compounds led to caspase dependent apoptosis through activation of intrinsic mitochondrial and extrinsic death receptor pathways. Collectively, these data show that combined epigenetic therapy, using HDAC and DNA methyltransferase inhibitors, may be a promising therapeutic approach for NK-LGL leukaemia.
نوع الوثيقة: text
اللغة: unknown
Relation: https://digitalcommons.pcom.edu/scholarly_papers/297
الاتاحة: https://digitalcommons.pcom.edu/scholarly_papers/297
رقم الانضمام: edsbas.65C1F5F
قاعدة البيانات: BASE