Ursolic acid-mediated apoptosis of K562 cells involves Stat5/Akt pathway inhibition through the induction of Gfi-1.

ABSTRACT: Ursolic acid (UA) is a promising natural compound for cancer prevention and therapy. We previously reported that UA induced apoptosis in CML-derived K562 cells. Here we show that the apoptotic process is accompanied by down-regulation of Bcl-xL and Mcl-1 expression and dephosphorylation of Bad. These events are associated with Stat5 inhibition, which is partially mediated through elevated expression of transcriptional repressor Gfi-1. Gfi-1 knockdown using siRNA abrogates the ability of UA to decrease Stat5b expression and attenuates apoptosis induction by UA. We also demonstrate that UA suppresses the Akt kinase activity by inhibiting Akt1/2 expression, which correlates with Stat5 inhibition. Stat5 activity inhibited by a chemical inhibitor or siRNA, Akt1/2 mRNA expression is suppressed.

SUBMITTER: Lin Z 

PROVIDER: S-EPMC5025887 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature