Identification of 20( S )-Ginsenoside Rh2 as a Potential EGFR Tyrosine Kinase Inhibitor.

As the main active ingredients of Panax ginseng , ginsenosides possess numerous bioactivities. Epidermal growth factor receptor (EGFR) was widely used as a valid target in anticancer therapy. Herein, the EGFR targeting activities of 20( S )-ginsenoside Rh2 (20( S )-Rh2) and the relationship of their structure-activity were investigated. Homogeneous time-resolved fluorescence assay showed that 20( S )-Rh2 significantly inhibited the activity against EGFR kinase. 20( S )-Rh2 was confirmed to effectively inhibited cell proliferation in a dose-dependent manner by MTT assay. Furthermore, quantitative real-time PCR and western blotting analysis revealed that 20( S )-Rh2 inhibited A549 cells growth via the EGFR-MAPK pathway. Meanwhile, 20( S )-Rh2 could promote cell apoptosis, block cell cycle, and reduce cell migration of A549 cells, respectively. In silico , the result suggested that both hydrophobic interactions and hydrogen-bonding interactions could contribute to stabilize their binding. Molecular dynamics simulation showed that the side chain sugar moiety of 20( S )-Rh2 was too flexible to be fixed at the active site of EGFR. Collectively, these findings suggested that 20( S )-Rh2 might serve as a potential EGFR tyrosine kinase inhibitor.