Key Features of the Paper
STUDY AIM
To explore the underlying mechanism of 4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR) and the effect of ATPR on autophagy of APL cells.
Methods
The following procedures were used: cell cycle analysis, differentiation marker analysis, quantitative real-time PCR analysis, transmission electron microscopy.
Results
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.
Conclusion
These results suggested that autophagy play an important role in ATPR-induced cell differentiation, which may provide a novel approach to cure APL patients.