Anti-proliferative Effect of Brucea javanica Fruit Extract Against Human Hepatocarcinoma Cell Lines and Its Mechanism

The fruits of Brucea javanica (Linn.) Merr (Simaroubaceae) are used as herbal remedies for treatment of human amebiasis, as well as for cancer in Chinese folklore. Here, we studied the anti-proliferative activity of the extract from fruit of B. javanica (BJE) and the fraction (BJEF5) against Hep G2 human hepatocarcinoma cells, and explored their mechanisms. From these studies, BJE showed growth inhibitory activity effect by the MTT assay in a dose-dependent manner with an IC₅₀ value of 1.56±1.02µg/mL, and by HP20 resin chromatography, the fraction (BJEF5) of elute washing by 50% EtOH showed more potent effect in a dose-dependent manner with an IC₅₀ value of 0.44±0.02µg/mL. However, cell cytotoxic activity was not observed in the peripheral blood mononuclear cell (PBMC) treated with BJE or BJEF5 less than 30µg/mL. Results from flow cytometry analysis also showed, BJE and BJEF5 induced cell cycle arrest in G1 phase as compared with the control groups, and the β-catenin transcription activity was inhibited in Hep G2 cells when treated with BJE and BJEF5, respectively. Furthermore, western blot analysis indicated that BJE and BJEF5 significantly reduced c-Myc, cyclin D1 protein levels leading to cell cycle arrest, and survivin protein level leading to apoptosis in a dose-dependent manner, respectively. Therefore, the BJE or BJEF5 deserves further exploration for it's use as a potential agent in the therapy for hepatocellular carcinoma (HCC).

Keywords: antiproliferation, Brucea javanica, hepatocarcinoma

Acknowledgement: The authors would like to thank the Ministry of Economic Affairs for the financial support of this research under contract No. MOEA 99-EC-17-A-02–04–0317.