ROS play an important role in ATPR inducing differentiation and inhibiting proliferation of leukemia cells by regulating the PTEN/PI3K/AKT signaling pathway

Abstract Background: Acute 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-ph...

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Autores principales:	Feng,Yubin, Hua,Xiaoxiao, Niu,Ruowen, Du,Yan, Shi,Congjian, Zhou,Renpeng, Chen,Fei-Hu
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2019
Materias:	Acute myeloid leukemia Differentiation Proliferation ATPR ROS PTEN/PI3K/AKT
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100224
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spelling	oai:scielo:S0716-976020190001002242019-10-10ROS play an important role in ATPR inducing differentiation and inhibiting proliferation of leukemia cells by regulating the PTEN/PI3K/AKT signaling pathwayFeng,YubinHua,XiaoxiaoNiu,RuowenDu,YanShi,CongjianZhou,RenpengChen,Fei-Hu Acute myeloid leukemia Differentiation Proliferation ATPR ROS PTEN/PI3K/AKT Abstract Background: Acute 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. Methods: In 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. Results: ATPR 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 24 h 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. Conclusions: Our observations could help to develop new drugs targeting the ROS/PTEN/PI3K/Akt pathway for the treatment of AML.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.52 20192019-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100224en10.1186/s40659-019-0232-9
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Acute myeloid leukemia Differentiation Proliferation ATPR ROS PTEN/PI3K/AKT
spellingShingle	Acute myeloid leukemia Differentiation Proliferation ATPR ROS PTEN/PI3K/AKT Feng,Yubin Hua,Xiaoxiao Niu,Ruowen Du,Yan Shi,Congjian Zhou,Renpeng Chen,Fei-Hu ROS play an important role in ATPR inducing differentiation and inhibiting proliferation of leukemia cells by regulating the PTEN/PI3K/AKT signaling pathway
description	Abstract Background: Acute 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. Methods: In 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. Results: ATPR 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 24 h 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. Conclusions: Our observations could help to develop new drugs targeting the ROS/PTEN/PI3K/Akt pathway for the treatment of AML.
author	Feng,Yubin Hua,Xiaoxiao Niu,Ruowen Du,Yan Shi,Congjian Zhou,Renpeng Chen,Fei-Hu
author_facet	Feng,Yubin Hua,Xiaoxiao Niu,Ruowen Du,Yan Shi,Congjian Zhou,Renpeng Chen,Fei-Hu
author_sort	Feng,Yubin
title	ROS play an important role in ATPR inducing differentiation and inhibiting proliferation of leukemia cells by regulating the PTEN/PI3K/AKT signaling pathway
title_short	ROS play an important role in ATPR inducing differentiation and inhibiting proliferation of leukemia cells by regulating the PTEN/PI3K/AKT signaling pathway
title_full	ROS play an important role in ATPR inducing differentiation and inhibiting proliferation of leukemia cells by regulating the PTEN/PI3K/AKT signaling pathway
title_fullStr	ROS play an important role in ATPR inducing differentiation and inhibiting proliferation of leukemia cells by regulating the PTEN/PI3K/AKT signaling pathway
title_full_unstemmed	ROS play an important role in ATPR inducing differentiation and inhibiting proliferation of leukemia cells by regulating the PTEN/PI3K/AKT signaling pathway
title_sort	ros play an important role in atpr inducing differentiation and inhibiting proliferation of leukemia cells by regulating the pten/pi3k/akt signaling pathway
publisher	Sociedad de Biología de Chile
publishDate	2019
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100224
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ROS play an important role in ATPR inducing differentiation and inhibiting proliferation of leukemia cells by regulating the PTEN/PI3K/AKT signaling pathway

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