In the present study, we investigate the anti-cancer activity and mechanism of caudatin, the C-21 steroidal glycosides, on human hepatoma cell line HepG2. The MTT assay and flow cytometry were used to evaluate HepG2 cell proliferation and cell cycle. Annexin-V/PI and DAPI staining were used to investigate cell apoptosis. Western blotting analysis was used to evaluate the expression levels of proteins. It is found that caudatin inhibits HepG2 cell growth and induces of G0/G1 phase arrest in a dose dependent manner, which is associated with a decreased in the expression of cyclinD1 and increased the levels of p21 and p53. HepG2 cells dealing with caudatin showed typical characteristics of apoptosis. Western blotting analysis indicated that the levels of Bcl-2 were down-regulated after caudatin treatment, whereas the expression of Bax was up-regulated. Furthermore, caudatin-induced apoptosis was accompanied by activation of caspase-3, -9, and poly(ADP-Ribose) Polymerase (PARP). Treatment with caudatin also induced phosphorylation of extracellular-signal regulating kinase (ERK) and c-Jun N-terminal kinase (JNK). These results demonstrate that caudatin inhibits cell proliferation via DNA synthesis reduction and induces caspase-dependent apoptosis in HepG2 cell. Activation of ERK and JNK may be involved in caudatin-induced hepatoma cell apoptosis.

Targeting angiogenesis is considered an effective strategy for treating the expansion and metastasis of tumors. The aim of this study is to assess the effects of perifosine, an inhibitor of Akt, on cell proliferation, apoptosis, angiogenesis, and VEGF-induced cell migration in cultured human umbilical vein endothelial cells (HUVECs) in vitro. MTT and cell cycle analysis results indicated that perifosine inhibited the growth of HUVECs in a dose-dependent manner, arrested cell cycle progression at the G(2) phase with regulation the expression of p21 and cyclinB1. Apoptosis induced by the higher concentrations of perifosine in HUVECs was also observed. In addition, tube formation of HUVECs and VEGF-induced cell migration were markedly inhibited by perifosine. Western blotting analysis of cell signaling molecules indicated that perifosine inhibited ERK and p38 phosphorylation in HUVECs. These results suggest that perifosine exerts anti-angiogenic activity in HUVECs and is a promising agent for treatment of angiogenesis related-diseases.