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The Pharmacological Inhibition of ERK5 Enhances Apoptosis in Acute Myeloid Leukemia Cells
Int J Stem Cells 2018;11:227-234
Published online November 30, 2018;  
© 2018 Korean Society for Stem Cell Research.

Changhee Kang1, Jong Soo Kim1, C-Yoon Kim1, Eun-Young Kim2,3, Hyung-Min Chung1

1Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Korea
2Stem Cell Research Center, Jeju National University, Jeju, Korea
3Mirae Cell Bio Co. LTD, Seoul, Korea
Correspondence to: Hyung-Min Chung
Department of Stem Cell Biology, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea
Tel: +82-2-2049-6232, Fax: +82-2-455-9015
E-mail: stemchung@gmail.com
Received July 12, 2018; Revised August 13, 2018; Accepted August 14, 2018.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Acute myeloid leukemia (AML) is a fatal hematological malignancy which is resistant to a variety of chemotherapy drugs. Extracellular signal-regulated kinase 5 (ERK5) plays a novel role in chemoresistance in some cancer cells and this pathway is a central mediator of cell survival and apoptotic regulation. The aim of this study was to investigate the effect of ERK5 inhibitor, XMD8-92, on proliferation and apoptosis in AML cell lines. Findings showed that XMD8-92 inhibited the activation of ERK5 by G-CSF and decreased the expression of c-Myc and Cyclin D1. The treatment of XMD8-92 reduced the phosphorylation of ERK5 leading to a distinct inhibition of cell proliferation and increased apoptosis in Kasumi-1 and HL-60 cells. Taken together, our study suggests that the inhibition of ERK5 by XMD8-92 can trigger apoptosis and inhibit proliferation in AMLs. Therefore, the inhibition of ERK5 may be an effective adjuvant in AML chemotherapy.
Keywords : ERK5, XMD8-92, Cell cycle, Apoptosis, Acute myeloid leukemia


November 2018, 11 (2)