Research Paper Volume 12, Issue 16 pp 16083—16098
Chidamide, a histone deacetylase inhibitor, inhibits autophagy and exhibits therapeutic implication in chronic lymphocytic leukemia
- 1 Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
- 2 Key Laboratory of Hematology of Nanjing Medical University, Nanjing 210029, China
- 3 Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing 210029, China
Received: November 8, 2019 Accepted: June 4, 2020 Published: August 27, 2020https://doi.org/10.18632/aging.103536
How to Cite
Copyright © 2020 Kong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Novel agents have made the management of chronic lymphocytic leukemia (CLL) more promising and personalized. However, long-term treatment is still warranted which may result in toxicity and resistance. Thus, new combination therapy may help achieve deeper remission and limited-duration therapy. Histone deacetylase inhibitors (HDACi) can affect many tumors by modulating key biological functions including autophagy. Studies have shown that some novel targeted agents including ibrutinib induce autophagy. This study aimed to explore the effect of oral HDAC inhibitor, chidamide, on CLL cells as well as the role of autophagy in this process. Here, we showed that autophagy flux in CLL cells was inhibited by chidamide via post-transcriptional modulation and chidamide had cytostatic and cytotoxic effects on CLL cells. Besides, the pro-survival role of autophagy in CLL cells was validated by using autophagy inhibitor and knocking down critical autophagy gene. Notably, a combination of chidamide and ibrutinib showed significant synergism and downregulated ibrutinib-induced autophagy. This work highlights the therapeutic potential of chidamide via its effect on autophagy, especially in combination with ibrutinib.
BTK: Bruton’s tyrosine kinase; CHI: chidamide; CHX: cycloheximide; CI: combination index; CLL: chronic lymphocytic leukemia; CQ: chloroquine; HDACi: histone deacetylase inhibitors; IB: ibrutinib; PTCL: peripheral T-cell lymphoma.