The Pharmacological Inhibition of ERK5 Enhances Apoptosis in Acute Myeloid Leukemia Cells
- Author:
Changhee KANG
1
;
Jong Soo KIM
;
C Yoon KIM
;
Eun Young KIM
;
Hyung Min CHUNG
Author Information
- Publication Type:Original Article
- Keywords: ERK5; XMD8-92; Cell cycle; Apoptosis; Acute myeloid leukemia
- MeSH: Apoptosis; Cell Cycle; Cell Line; Cell Proliferation; Cell Survival; Cyclin D1; Drug Therapy; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; HL-60 Cells; Humans; Leukemia, Myeloid, Acute; Mitogen-Activated Protein Kinase 7; Phosphorylation
- From:International Journal of Stem Cells 2018;11(2):227-234
- CountryRepublic of Korea
- Language:English
- 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.
