LAUSR

BACKGROUND Zerumbone (ZER) possesses potent antiproliferative, apoptotic, and antiangiogenic functions in a variety of cancer cells. Cisplatin (CIS), a well-known chemotherapeutic drug, is effective against different types of cancers. However, the combined effect of ZER and CIS on hepatocellular carcinoma remains unknown. OBJECTIVE The present study is attempted to examine the effectiveness of the combination of ZER and CIS in liver cancer in vitro using the hepatocellular carcinoma Huh-7 cell line. METHODS Effect of ZER, CIS, and their Combination therapy on cell viability and cytotoxicity was assessed by MTT and LDH leakage assays. Cell cycle and apoptosis analysis were performed by flow cytometry. Quantitative real-time PCR was used to examine the M RNA expression of genes involved in apoptosis, angiogenesis, and invasion. Caspase activities were performed by commercial kit methods in the Huh-7 cell line. RESULTS Cells exposed to ZER, CIS individually, and both together significantly inhibited cell proliferation with an IC50 values of 10 µM for ZER and 3µM for CIS. The combination treatment of ZER and CIS revealed a synergistic effect with CI value < 1. CIS treatment either alone or in combination with ZER caused cell cycle arrest at the S phase. More importantly, ZER combined with CIS exhibited synergistic effects by up-regulation of Bax/Bcl-2ratio, leading to caspase cascade activation. CONCLUSION In conclusion, the current study indicates that the treatment of ZER combined with CIS in human liver cancer cells exerts synergistic effects on cell growth inhibition, apoptosis induction, angiogenesis and invasion through modulating gene expression.