Chamaejasmenin E from Stellera chamaejasme induces apoptosis of hepatocellular carcinoma cells by targeting c-Met in vitro and in vivo

Hepatocellular carcinoma (HCC), the most prevalent liver cancer, is considered one of the most lethal malignancies with a dismal outcome. There is an urgent need to find novel therapeutic approaches to treat HCC. At present, natural products have served as a valuable source for drug discovery. Here, we obtained five known biflavones from the root of Stellera chamaejasme and evaluated their activities against HCC Hep3B cells in vitro. Chamaejasmenin E (CE) exhibited the strongest inhibitory effect among these biflavones. Furthermore, we found that CE could suppress the cell proliferation and colony formation, as well as the migration ability of HCC cells, but there was no significant toxicity on normal liver cells. Additionally, CE induced mitochondrial dysfunction and oxidative stress, eventually leading to cellular apoptosis. Mechanistically, the potential target of CE was predicted by database screening, showing that the compound might exert an inhibitory effect by targeting at c Met. Next, this result was confirmed by molecular docking, cellular thermal shift assay (CETSA), as well as RTPCR and Western blot analysis. Meanwhile, CE also reduced the downstream proteins of c-Met in HCC cells. In concordance with above results, CE is efficacious and non-toxic in tumor xenograft model. Taken together, our findings revealed an underlying tumor-suppressive mechanism of CE, which provided a foundation for identifying the target of biflavones.

Automated summary

The study found that the biflavone CE from Stellera chamaejasme root exhibited strong inhibitory effects against HCC Hep3B cells. This inhibition may be achieved by targeting c Met. CE also suppressed cell proliferation, colony formation, and migration ability of HCC cells, and showed efficacy without toxicity in a tumor xenograft model.