Figure 5.

Model showing the proposed molecular mechanism of diosgenin-induced mitochondria-dependent apoptosis via checkpoint kinase activation in breast cancer cells. In this model, solid arrows show positive activation pathways determined in our studies. Gray arrows indicate functions reported previously [27]. The model suggests that diosgenin phosphorylates (activates) Chk1 at Ser345, leading to inactivation of the downstream target protein, phospho-Cdc25C^Ser216. Alternatively, inhibition of Cdc2/cyclin B via phosphorylated Chk1-Cdc25C signaling results in G2/M phase arrest that can cause p53-independent p21 activation, as shown in Hs578T cells.