Blumea balsamifera Extract Induces Apoptosis and Inhibit Cell Migration on HepG2 Hepatocellular Carcinoma: An Integrated Experimental and Computational Study

Hepatocellular carcinoma (HCC) is one of the most aggressive types of cancer and requires alternative therapeutic strategies beyond current treatments. Blumea balsamifera is a medicinal plant with potential anticancer properties that may offer a novel approach for HCC treatment. This study aimed to evaluate the anti-HCC activity of B. balsamifera extract through an integrated experimental and computational approach. Experimental assays were performed to assess cytotoxicity, apoptosis induction, mitochondrial membrane potential, and cell migration, while computational analyses were applied to predict the molecular mechanisms involved using network pharmacology, molecular docking, and molecular dynamic simulation. The extract demonstrated cytotoxic activity against HepG2 cells (IC₅₀ = 199.09 ± 11.86 µg/mL) and significantly induced apoptosis in a dose-dependent manner, with the IC₅₀ concentration triggering apoptosis in more than 80% of cells. In addition, B. balsamifera extract markedly inhibited HepG2 cell migration, with 74% of the wound gap remaining open at the IC₅₀ concentration. Network pharmacology analysis further predicted that the bioactive compounds of B. balsamifera may act by targeting key HCC-related proteins involved in cell death and migration pathways, including TOP1, AKT1, PPM1D, SRC, AKR1C2, DNMT1, and PTH. Collectively, these findings provide both experimental evidence and computational insights supporting the potential of B. balsamifera as a promising natural therapeutic candidate for hepatocellular carcinoma. HIGHLIGHTS Blumea balsamifera extract induces apoptosis and inhibits migration in HepG2 cells. Network pharmacology identified nine active compounds targeting 190 HCC-related proteins. Docking and MD simulations confirmed stable binding to key targets (TOP1, AKT1, PPM1D, SRC, AKR1C2, DNMT1, PTH). Findings support balsamifera as a potential multi-target natural therapeutic for HCC. GRAPHICAL ABSTRACT