Journal
BIOLOGICAL RESEARCH
Volume 52, Issue -, Pages -Publisher
SOC BIOLGIA CHILE
DOI: 10.1186/s40659-019-0232-9
Keywords
Acute myeloid leukemia; Differentiation; Proliferation; ATPR; ROS; PTEN; PI3K; AKT
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Funding
- National Major Scientific and Technological Special Project for Significant New Drugs Development [2011ZX09401]
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BackgroundAcute myeloid leukemia (AML) is an aggressive and mostly incurable hematological malignancy with frequent relapses after an initial response to standard chemotherapy. Therefore, novel therapies are urgently required to improve AML clinical outcomes. 4-Amino-2-trifluoromethyl-phenyl retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, has been proven to show biological anti-tumor characteristics in our previous studies. However, its potential effect on leukemia remains unknown. The present research aims to investigate the underlying mechanism of treating leukemia with ATPR in vitro.MethodsIn this study, the AML cell lines NB4 and THP-1 were treated with ATPR. Cell proliferation was analyzed by the CCK-8 assay. Flow cytometry was used to measure the cell cycle distribution and cell differentiation. The expression levels of cell cycle and differentiation-related proteins were detected by western blotting and immunofluorescence staining. The NBT reduction assay was used to detect cell differentiation.ResultsATPR inhibited cell proliferation, induced cell differentiation and arrested the cell cycle at the G0/G1 phase. Moreover, ATPR treatment induced a time-dependent release of reactive oxygen species (ROS). Additionally, the PTEN/PI3K/Akt pathway was downregulated 24h after ATPR treatment, which might account for the anti-AML effects of ATPR that result from the ROS-mediated regulation of the PTEN/PI3K/AKT signaling pathway.ConclusionsOur observations could help to develop new drugs targeting the ROS/PTEN/PI3K/Akt pathway for the treatment of AML.
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