AICAR and Decitabine Enhance the Sensitivity of K562 Cells to Imatinib by Promoting Mitochondrial Activity
- PDF / 838,654 Bytes
- 8 Pages / 595.276 x 841.89 pts (A4) Page_size
- 81 Downloads / 185 Views
40(5):871-878,2020
871
AICAR and Decitabine Enhance the Sensitivity of K562 Cells to Imatinib by Promoting Mitochondrial Activity Xiao-ying ZHU1, Wen LIU1, Hai-tao LIANG1, Ling TANG1, Ping ZOU1, Yong YOU1, Xiao-jian ZHU2# 1 Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China 2 Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China Huazhong University of Science and Technology 2020
Summary: Although the advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the survival of patients with chronic myeloid leukaemia (CML), acquired drug resistance and TKI-insensitive leukaemic stem cells (LSCs) remain major obstacles to a CML cure. In recent years, the reprogramming of mitochondrial metabolism has emerged as a hallmark of cancers, including CML, and in turn may be exploited for therapeutic purposes. Here, we investigated the effects of several drugs on the mitochondrial function of the CML cell line K562 and found that 5-aminoimidazole-4-carboxamide ribotide (AICAR) and decitabine could effectively increase the ATP content and mitochondrial biogenesis. In addition, these two drugs induced cell cycle arrest and a decrease in colony-forming capacity and promoted K562 cell differentiation. Moreover, we demonstrated that treatment with AICAR or decitabine enhanced the sensitivity of K562 cells to imatinib, as evidenced by a combination treatment assay. Altogether, our findings indicate that TKIs combined with mitochondrial regulation may provide a therapeutic strategy for the treatment of CML. Key words: chronic myeloid leukaemia; mitochondrial activity; 5-aminoimidazole-4-carboxamide ribotide (AICAR); decitabine
Chronic myeloid leukaemia (CML) is a malignant clonal disease originating from the reciprocal translocation of chromosomes 9 and 22 (the Philadelphia chromosome) in haematopoietic stem cells, resulting in the expression of the constitutively active tyrosine kinase BCR-ABL1[1]. The introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs) has dramatically improved the survival of CML patients in the chronic phase and made their life expectancy similar to that of the general population[2, 3]. However, acquired drug resistance and persistent CML leukaemic stem cells (CML LSCs) remain challenge to the cure of the vast majority of patients[4–6], and the risk of progression to the accelerated phase or blast crisis, in which the cancer responds poorly to TKIs, is still an intractable clinical issue[7]. Thus, the discovery of novel therapeutic strategies and the application of combination therapy still require intensive research efforts. Mitochondria, as the energy powerhouse and main metabolite source of the cell, play an essential role in cell growth and development[8]. In fact, a Xiao-ying ZHU, E-mail: [email protected] # Corresponding author, E-mail: [email protected]
large number of researchers have focused on the function of mit
Data Loading...
