Timosaponin A­III induces autophagy of T­cell acute lymphoblastic leukemia Jurkat cells via inhibition of the PI3K/Akt/mTOR pathway.

ABSTRACT

Timosaponin A­III (TAIII) is a saponin isolated from anemarrhena asphodeloides and possesses the inhibitory effect on proliferation of multiple tumor cells. In the present study, the antitumor effect of TAIII and its underlying molecular mechanisms were investigated in vitro in T­cell acute lymphoblastic leukemia (T­ALL) Jurkat cells. The results demonstrated that TAIII inhibits the viability of Jurkat cells in a time­ and dose­dependent manner, and induces apoptosis of Jurkat cells in a dose­dependent manner. Transmission electron microscopy demonstrated the formation of numerous autophagosomes in TAIII­treated Jurkat cells. Furthermore, monodansylcadaverine (MDC)­labeled autophagic vacuoles were observed following TAIII treatment by an inverted fluorescence microscope and MDC accumulation increased notably in TAIII treatment groups in a concentration­dependent manner. B­cell lymphoma­2 (Bcl­2)­associated X (Bax) was upregulated while Bcl­2 was reduced following TAIII treatment, indicating that the pro­apoptotic mechanism of TAIII may be associated with upregulation of Bax. Further investigation revealed that TAIII promotes the expression of autophagy­associated proteins Beclin 1 and LC3­II, and inhibits the phosphoinositide 3­kinase/Akt/mechanistic target of rapamycin kinase pathway. The present study revealed that the antitumor activity of TAIII was primarily achieved by the induction of cell apoptosis and autophagy, indicating a promising potential as a novel effective reagent against T­ALL.