Abstract
BACKGROUND: Adenanthin, a diterpenoid isolated from the leaves of Rabdosia adenantha, has anti-tumor activities. However, its role and mechanism in pancreatic cancer are unclear. This study aims to elucidate the mechanism of adenanthin induced death of pancreatic cancer cells by regulating hydrogen peroxide (H(2)O(2)) and reactive oxygen species (ROS) levels. METHODS: Adenanthin was used to detect its cell activity on pancreatic cancer cells (Aspc-1) using the Cell Counting Kit-8 (CCK-8) and colony forming assays. Hoechst 33258 fluorescence staining and flow cytometry related experiments were used to detect its impact on apoptosis and cell cycle of Aspc-1 cells. Western blot was used to detect the expression of cycle and apoptosis related proteins, and the concentration of H(2)O(2) and ROS in Aspc-1 cells were measured by content determination kit. A mouse tumor transplantation model was established and the expression of related proteins after administration of adenanthin was detected. RESULTS: Adenanthin can inhibit the proliferation and induce apoptosis of pancreatic cancer cells. The results of propidium iodide (PI) single staining flow cytometry showed that adenanthin significantly blocked Aspc-1 cells in the S phase and G2/M phase. Further exploration of its mechanism found that adenanthin significantly increased the content of H(2)O(2) and ROS in cells, and realized the inhibitory effect on pancreatic cancer cells by regulating apoptosis and cyclin. The transplanted tumor model in mice was consistent with the results of cell experiments. CONCLUSIONS: In pancreatic cancer, adenanthin can significantly increase the content of H(2)O(2) and ROS, induce apoptosis and cycle arrest of pancreatic cancer cells, and ultimately play a role in treating pancreatic cancer. Therefore, adenanthin is expected to become a new drug against pancreatic cancer.