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Author Li, Yue ♦ Li, Ge ♦ Wang, Ke ♦ Xie, Ya-Ya ♦ Zhou, Ren-P.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ARSENIC ♦ CATTLE ♦ CELL DIFFERENTIATION ♦ IN VITRO ♦ IN VIVO ♦ MYELOID LEUKEMIA ♦ PHOSPHATES ♦ POLYMERASE CHAIN REACTION ♦ POLYMERASES ♦ RETINOIC ACID ♦ RNA ♦ TRANSMISSION ELECTRON MICROSCOPY
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 differentiation in NB4 cells. • Notch1 signaling is involved in ATPR-induced autophagy and differentiation in NB4 cells.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2017-03-15
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 319


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