Gastrointestinal tumors are the most frequently diagnosed malignancy and the second highest contributor to cancer mortality. Cyclopeptides are rarely isolated from ginseng because they are often present at low concentrations in a complex matrix. In the current study, seven novel ginseng cyclopeptides (GCPs) were isolated and their anti-tumor potency was explored. Anti-proliferative test results show that the (GCP-1)∼[cyclo-(L-Trp-L-Glu-L-Phe-L-Thr)] peptide display the best anti-proliferative activity in gastric cancer SGC-7901 cells in vitro, with an IC50 value of 37.8 ± 3.13 μM. Flow cytometry analysis shows that GCP-1 (7.56–189 μM) clearly induce early apoptosis and mitochondrial membrane potential collapse, and block the cells at the G0/G1 phase. A further study revealed that GCP-1 induces apoptosis by activating the caspases, suppressing the thioredoxin (Trx) system and subsequently activating a number of Trx-dependent pathways, including those involving apoptotic signal-regulating kinase 1 (ASK1) and mitogen-activated protein kinases (MAPKs). The cyclopeptides in ginseng are an important resource for the research and development of anti-neoplastic drugs.
