Polyphyllin I induces apoptosis and autophagy via modulating JNK and mTOR pathways in human acute myeloid leukemia cells.

Polyphyllin I (PPI), a bioactive component extracted from Paris polyphylla, was reported to have potent anticancer activities in previous studies. However, there were few reports on the effects and underlying mechanism of PPI in human acute myeloid leukemia cells. The present study demonstrated that PPI had an inhibitory effect through inducing apoptosis and autophagy in THP-1 and NB4 cells. PPI induced apoptosis via activating JNK pathway, as evidenced by the decreased Bcl-2 levels and increased Bax, cleaved-caspase-3 and phosphorylated-JNK expressions. In addition, PPI promoted autophagy as evidenced with increased expressions of LC3-II and Beclin-1 in western blot and autophagic vacuoles in MDC staining, which was associated with the inhibition of AKT-mTOR pathway. Furthermore, JNK inhibitor SP600125 and autophagy inhibitor 3-MA were employed to evaluate the role of apoptosis and autophagy in PPI-induced cell death. We found that autophagy and apoptosis were both causes of cell death induced by PPI. These data suggested that PPI could be a potent therapeutic agent for the treatment of human acute myeloid leukemia.