Ginsenoside F2 induces apoptosis in humor gastric carcinoma cells through reactive oxygen species-mitochondria pathway and modulation of ASK-1/JNK signaling cascade in vitro and in vivo

Ginsenoside F-2 (F-2) is a potential bioactive metabolite of major ginsenosides. The potential anti-cancer effect of F-2 in gastric cancer cells has not been appraised. This study investigated the effects of F-2 on the production of reactive oxygen species (ROS). We also investigated the in vitro and in vivo effects of F-2 on the downstream signaling pathways leading to apoptosis in human gastric cancer cells. The in vitro data revealed that F-2 induces ROS accumulation followed by a decrease in mitochondrial transmembrane potential (MTP), and the release of cytochrome c (cyto c), which induced the caspase-dependent apoptosis. Further assay indicated that modulation of ASK-1/JNK pathway contributes to apoptosis. In vivo, F-2 exhibits the obvious anti-cancer effect compared with cisplatin with no obvious toxicity. Jointly, these results suggest that F-2 induces apoptosis by causing an accumulation of ROS and activating the ASK-1/JNK signaling pathway. This provides further support for the use of F-2 as a novel anticancer therapeutic candidate. (C) 2013 Elsevier GmbH. All rights reserved.