Corylin inhibits liver cancer cell growth through the endogenous apoptosis and mitophagy

Background: Corylin is a bioactive extract of Psoralea corylifolia L. with reported antioxidant, anti-tumor, and anti-inflammatory effects. Its anti-tumor effects have been investigated, but mechanistic explanations are lacking. This study mainly focuses on the role and mechanism of Corylin in inducing liver cancer cell death. Methods: The effects of Corylin on liver cancer cell proliferation were analyzed using crystal violet staining and cell counting kit-8 (CCK-8) assays. Nuclear changes were detected via Hoechst staining, while apoptosis levels were assessed using Annexin V- fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. Changes in mitochondrial membrane potential and reactive oxygen species (ROS) levels were analyzed using JC-1 and tetramethylrhodamine methyl ester (TMRM) staining combined with flow cytometry. Immunofluorescence staining and Western blot (WB) experiments assessed alterations in apoptosis- and autophagy-related proteins. Finally, the effects of Corylin on liver cancer cells in vivo were validated by establishing a subcutaneous tumor model. Results: In this study, we found that Corylin had a significant anti-liver cancer effect and significantly increased the apoptosis level of liver cancer cells. Additionally, Corylin was found to significantly reduce mitochondrial membrane potential and significantly increase ROS release. It was also observed that Corylin significantly influenced autophagy levels in liver cancer cells. Further analysis revealed that Corylin induced mitophagy, with the increase in autophagy levels being directly proportional to the rise in apoptosis levels. Finally, the establishment of a subcutaneous tumor-bearing model showed that Corylin also had a significant anti-liver cancer effect in vivo. Conclusions: The above results demonstrated that Corylin mainly caused the death of liver cancer cells through the endogenous apoptosis and mitophagy pathway and had great potential as an anti-liver cancer drug.