We investigated the molecular mechanisms of cell cycle arrest and apoptotic death induced by Solanum lyratum extracts (SLE) or
diosgenin in WEHI-3 murine
leukemia cells in vitro and antitumor activity in vivo.
Diosgenin is one of the components of SLE. Our study showed that SLE and
diosgenin decreased the viable WEHI-3 cells and induced G(0)/G(1) phase arrest and apoptosis in concentration- or time-dependent manners. Both
reagents increased the levels of ROS production and decreased the mitochondrial membrane potential (ΔΨ(m)). SLE- and
diosgenin-triggered apoptosis is mediated through modulating the extrinsic and intrinsic signaling pathways. Intriguingly, the p53 inhibitor (
pifithrin-α), anti-
Fas ligand (FasL) mAb, and specific inhibitors of
caspase-8 (
z-IETD-fmk),
caspase-9 (
z-LEHD-fmk), and
caspase-3 (
z-DEVD-fmk) blocked SLE- and
diosgenin-reduced cell viability of WEHI-3 cells. The in vivo study demonstrated that SLE has marked antitumor efficacy against
tumors in the WEHI-3 cell allograft model. In conclusion, SLE- and
diosgenin-induced G(0)/G(1) phase arrest and triggered extrinsic and intrinsic apoptotic pathways via p53 activation in WEHI-3 cells. SLE also exhibited antitumor activity in vivo. Our findings showed that SLE may be potentially efficacious in the treatment of
leukemia in the future.