adenanthin and Liver-Neoplasms

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.. 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.. 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.. 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.

Topics: Carcinoma, Hepatocellular; Cell Line, Tumor; Diterpenes, Kaurane; Humans; Killer Cells, Natural; Ligands; Liver Neoplasms

Adenanthin, a natural diterpenoid isolated from the leaves of Isodon adenanthus, has recently been reported to induce leukemic cell differentiation by targeting peroxiredoxins (Prx) I and II. On the other hand, increasing lines of evidence propose that these Prx proteins would become potential targets to screen drugs for the prevention and treatment of solid tumors. Therefore, it is of significance to explore the potential activities of adenanthin on solid tumor cells. Here, we demonstrate that Prx I protein is essential for the survival of hepatocellular carcinoma (HCC) cells, and adenanthin can kill these malignant liver cells in vitro and xenografts. We also show that the cell death-inducing activity of adenanthin on HCC cells is mediated by the increased reactive oxygen species (ROS) levels. Furthermore, the silencing of Prx I or Prx II significantly enhances the cytotoxic activity of adenanthin on HCC, whereas the ectopic expression of Prx I and Prx II but not their mutants of adenanthin-bound cysteines can rescue adenanthin-induced cytotoxicity in Prxs-silenced HCC cells. Taken together, our results propose that adenanthin targets Prx I/II to kill HCC cells and its therapeutic significance warrants to be further explored in HCC patients.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Hepatocellular; Cell Line, Tumor; Diterpenes, Kaurane; Hep G2 Cells; Humans; Isodon; Liver Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Oxidative Stress; Peroxiredoxins; Plant Leaves; Reactive Oxygen Species; RNA Interference; RNA, Small Interfering; Transplantation, Heterologous