標題: HDAC1,2 Knock-Out and HDACi Induced Cell Apoptosis in Imatinib-Resistant K562 Cells
作者: Chen, Shu-Huey
Chow, Jyh-Ming
Hsieh, Yao-Yu
Lin, Chun-Yu
Hsu, Kai-Wen
Hsieh, Wen-Shyang
Chi, Wei-Ming
Shabangu, Beished M.
Lee, Chia-Hwa
生物資訊及系統生物研究所
Institude of Bioinformatics and Systems Biology
關鍵字: imatinib;CML;histone deacetylase inhibitor;imatinib-resistant;CRISPR;Cas9
公開日期: 1-五月-2019
摘要: Since imatinib (Glivec or Gleevec) has been used to target the BCR-ABL fusion protein, chronic myeloid leukemia (CML) has become a manageable chronic disease with long-term survival. However, 15%-20% of CML patients ultimately develop resistance to imatinib and then progress to an accelerated phase and eventually to a blast crisis, limiting treatment options and resulting in a poor survival rate. Thus, we investigated whether histone deacetylase inhibitors (HDACis) could be used as a potential anticancer therapy for imatinib-resistant CML (IR-CML) patients. By applying a noninvasive apoptosis detection sensor (NIADS), we found that panobinostat significantly enhanced cell apoptosis in K562 cells. A further investigation showed that panobinostat induced apoptosis in both K562 and imatinib-resistant K562 (IR-K562) cells mainly via H3 and H4 histone acetylation, whereas panobinostat targeted cancer stem cells (CSCs) in IR-K562 cells. Using CRISPR/Cas9 genomic editing, we found that HDAC1 and HDAC2 knockout cells significantly induced cell apoptosis, indicating that the regulation of HDAC1 and HDAC2 is extremely important in maintaining K562 cell survival. All information in this study indicates that regulating HDAC activity provides therapeutic benefits against CML and IR-CML in the clinic.
URI: http://dx.doi.org/10.3390/ijms20092271
http://hdl.handle.net/11536/152390
ISSN: 1422-0067
DOI: 10.3390/ijms20092271
期刊: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume: 20
Issue: 9
起始頁: 0
結束頁: 0
顯示於類別:期刊論文