Premium
Optimal AraC‐Cytotoxicity to AML Cells Requires ERK5 Activity
Author(s) -
Zheng Ruifang,
Studzinski George P.
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25820
Subject(s) - cytarabine , myeloid leukemia , cytotoxicity , hl60 , cell cycle , programmed cell death , dna damage , cancer research , leukemia , cell cycle checkpoint , cell culture , downregulation and upregulation , u937 cell , cell , chemistry , apoptosis , microbiology and biotechnology , biology , dna , immunology , in vitro , biochemistry , gene , genetics
Cytarabine (AraC) has been the primary treatment agent for acute myeloid leukemia (AML) in the past 30 years, but the precise mechanism of its action is not completely known. Here we assessed the role of ERK5 in AraC‐induced cell death in AML cell lines HL60 and U937 using ERK5 inhibitors BIX02189 and XMD8‐92. We report that inhibition of MEK5/ERK5 activity reduces AraC‐induced cell death, DNA damage, the upregulated DNA damage biomarkers, and produced G2 phase cell cycle arrest. In addition, the pro‐survival protein P‐Bcl2 Ser70 was found to be associated with decreased AraC‐induced cell death following XMD8‐92 treatment, suggesting a regulatory role of ERK5 on Bcl2 phosphorylation. Our study shows that the full potency of AraC cytotoxicity requires optimal ERK5 activity, suggesting a novel role of ERK5 in cancer chemotherapy. J. Cell. Biochem. 118: 1583–1589, 2017. © 2016 Wiley Periodicals, Inc.