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Title: Autophagy contributes to 4-Amino-2-Trifluoromethyl-Phenyl Retinate-induced differentiation in human acute promyelocytic leukemia NB4 cells

Abstract

As a classic differentiation agent, all-trans retinoic acid (ATRA) has been widely used in treatment of acute promyelocytic leukemia (APL). However, clinical application of ATRA has limitations. Our previous studies suggested that 4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, could induce differentiation of APL cells in vivo and in vitro. To explore the underlying mechanism of ATPR, the effect of ATPR on autophagy of APL cells was observed in the present study. The results showed that the differentiation effect of ATPR on APL cells was accompanied with autophagy induction and PML-RARα degradation via activating Notch1 signaling pathway. Moreover, inhibition of autophagy using 3-methyladenine (3-MA) or small interfering RNA (siRNA) that targets essential autophagy gene ATG5 abrogated the ATPR-induced cell differentiation. Furthermore, when pretreated with DAPT, a γ-secretase inhibitor, the Notch1 signaling pathway was blocked in APL cells, followed by the reduction of ATPR-induced autophagy and differentiation. Taken together, these results suggested that autophagy play an important role in ATPR-induced cell differentiation, which may provide a novel approach to cure APL patients. - Highlights: • ATPR induces autophagy in APL cell line NB4 cells. • Autophagy induction is essential for cell differentiationmore » in NB4 cells. • Notch1 signaling is involved in ATPR-induced autophagy and differentiation in NB4 cells.« less

Authors:
; ; ; ; ; ; ; ;
Publication Date:
OSTI Identifier:
22690937
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 319; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARSENIC; CATTLE; CELL DIFFERENTIATION; IN VITRO; IN VIVO; MYELOID LEUKEMIA; PHOSPHATES; POLYMERASE CHAIN REACTION; POLYMERASES; RETINOIC ACID; RNA; TRANSMISSION ELECTRON MICROSCOPY

Citation Formats

Li, Yue, Li, Ge, Wang, Ke, Xie, Ya-Ya, Zhou, Ren-Peng, Meng, Yao, Ding, Ran, Ge, Jin-Fang, and Chen, Fei-Hu. Autophagy contributes to 4-Amino-2-Trifluoromethyl-Phenyl Retinate-induced differentiation in human acute promyelocytic leukemia NB4 cells. United States: N. p., 2017. Web. doi:10.1016/J.TAAP.2017.01.016.
Li, Yue, Li, Ge, Wang, Ke, Xie, Ya-Ya, Zhou, Ren-Peng, Meng, Yao, Ding, Ran, Ge, Jin-Fang, & Chen, Fei-Hu. Autophagy contributes to 4-Amino-2-Trifluoromethyl-Phenyl Retinate-induced differentiation in human acute promyelocytic leukemia NB4 cells. United States. https://doi.org/10.1016/J.TAAP.2017.01.016
Li, Yue, Li, Ge, Wang, Ke, Xie, Ya-Ya, Zhou, Ren-Peng, Meng, Yao, Ding, Ran, Ge, Jin-Fang, and Chen, Fei-Hu. 2017. "Autophagy contributes to 4-Amino-2-Trifluoromethyl-Phenyl Retinate-induced differentiation in human acute promyelocytic leukemia NB4 cells". United States. https://doi.org/10.1016/J.TAAP.2017.01.016.
@article{osti_22690937,
title = {Autophagy contributes to 4-Amino-2-Trifluoromethyl-Phenyl Retinate-induced differentiation in human acute promyelocytic leukemia NB4 cells},
author = {Li, Yue and Li, Ge and Wang, Ke and Xie, Ya-Ya and Zhou, Ren-Peng and Meng, Yao and Ding, Ran and Ge, Jin-Fang and Chen, Fei-Hu},
abstractNote = {As a classic differentiation agent, all-trans retinoic acid (ATRA) has been widely used in treatment of acute promyelocytic leukemia (APL). However, clinical application of ATRA has limitations. Our previous studies suggested that 4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative designed and synthesized by our team, could induce differentiation of APL cells in vivo and in vitro. To explore the underlying mechanism of ATPR, the effect of ATPR on autophagy of APL cells was observed in the present study. The results showed that the differentiation effect of ATPR on APL cells was accompanied with autophagy induction and PML-RARα degradation via activating Notch1 signaling pathway. Moreover, inhibition of autophagy using 3-methyladenine (3-MA) or small interfering RNA (siRNA) that targets essential autophagy gene ATG5 abrogated the ATPR-induced cell differentiation. Furthermore, when pretreated with DAPT, a γ-secretase inhibitor, the Notch1 signaling pathway was blocked in APL cells, followed by the reduction of ATPR-induced autophagy and differentiation. Taken together, these results suggested that autophagy play an important role in ATPR-induced cell differentiation, which may provide a novel approach to cure APL patients. - Highlights: • ATPR induces autophagy in APL cell line NB4 cells. • Autophagy induction is essential for cell differentiation in NB4 cells. • Notch1 signaling is involved in ATPR-induced autophagy and differentiation in NB4 cells.},
doi = {10.1016/J.TAAP.2017.01.016},
url = {https://www.osti.gov/biblio/22690937}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = ,
volume = 319,
place = {United States},
year = {Wed Mar 15 00:00:00 EDT 2017},
month = {Wed Mar 15 00:00:00 EDT 2017}
}