Actein enhances TRAIL effects on suppressing gastric cancer progression by activating p53/Caspase-3 signaling

Actein (ACT), isolated from the rthizomes of Cimicifuga foetida, is a triterpene glycoside, showing inhibitory role in breast cancer cells. However, the effects of ACT treatment on gastric cancer have little been known. Thus, the study is conducted to explore the in vitro and in vivo role of ACT in gastric cancer. And the interactions between ACT and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were investigated in gastric cancer cells. A synergistic effect of ACT and TRAIL combination on apoptosis induction in gastric cancer cells was observed. The cancer cells were insensitive to TRAIL single therapy. However, gastric cancer cells receiving ACT were sensitive to TRAIL-triggered apoptotic response by enhancing Caspases cleavage, due to elevation of decoy receptor 1 and 2 (DcR1 and DcR2) dependent on p53. Bcl-2 family members of Bcl-2 and Mcl-1, belonging to anti-apoptosis, were decreased, whereas Bad and Bak, as pro-apoptotic members, were increased for ACT and TRAIL combined treatment. Additionally, the mouse xenograft model suggested that ACT and TRAIL in combination markedly inhibited gastric cancer growth in comparison to ACT or TRAIL monotherapy without toxicity. The present study revealed a dramatically therapeutic strategy for promoting TRAIL-induced anti-cancer effects on gastric cancer cells via ACT combination.