The diterpenoid adenanthin upregulates the expression of natural killer group 2D receptor ligands in hepatocellular carcinoma cells

Objective: The natural killer (NK) group 2D (NKG2D) receptor plays a crucial role in NK cell-mediated anti-tumor immunity. NKG2D anti-proliferative effect is mediated by direct interactions of the receptor with its ligands that may be considered as a potential target for NK-based immunotherapeutic strategy in cancer cells. Methods: Here we report that a natural product adenanthin significantly promotes NKG2D ligands expression in hepatoma cells. The effect was determined using flow cytometry analysis. The activity of NK cell was evaluated by measuring its degranulation activity and cytotoxicity. Results: Our data indicates that the induction of NKG2D ligand binding to liver cancer cell surface receptors greatly improves the killing activity of NK cells against the cancer cells. Conclusions: This is the first report of a new mechanism anti-cancer effects of adenanthin mediated by an indirect activation of NK cells. Our data suggests that adenanthin may be used to sensitize NK cells in tumor immunotherapy.