Euphorbia helioscopia L. extract suppresses hepatitis B virus-related hepatocellular carcinoma via alpha serine/threonine-protein kinase and Caspase-3

Background: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HBV-HCC) has poor prognosis and high mortality rate. Euphorbia helioscopia L. (EHL) is a classic Chinese medicinal herb.

Aim: This study aimed to evaluate in vitro anti-HBV-HCC properties of EHL, and explore it targets in HBV-HCC based on molecular docking.

Methods: The anti-tumor effect of EHL on HBV-HCC was evaluated using the cell viability, migration, invasion, and Apoptosis of Hep 3B2.1-7 and HepG2.2.15 cells. Next, network pharmacological analysis was performed to predicted the key targets of EHL against HBV-HCC. Then the prognostic targets, including RAC-alpha serine/threonine-protein kinase (Akt1) and Caspase-3 (CASP3), were verified using molecular docking and rescue experiments.

Results: EHL exhibited inhibitory effects on cell proliferation/migration/invasion and induced cell Apoptosis. Network pharmacological analysis proposed 12 active compounds in EHL, which targeted 22 HBV-HCC-related genes. Akt1 and CASP3 were identified to be key targets for EHL against HBV-HCC. Akt1 and CASP3 had prognostic significance in liver Cancer. Overexpression of Akt1 and Caspase-3 inhibitor can counteract the EHL effect.

Conclusion: EHL can exert Anticancer effects on HBV-HCC by inhibiting migration/invasion, and inducing Apoptosis, which may be achieved through Akt1 and CASP3.

AKT1; CASP3; Hepatitis B virus; Herb; Liver cancer.