A garlic derivative S-allylcysteine suppresses liver tumor growth and metastasis by sensitizing chemotherapy

Abstract

Background and Objective: A garlic derivative S-allylcysteine (SAC) has anti-cancer effect in human prostate and colon cancers. We aimed to investigate the effect of SAC and combination of chemo-drug on tumorigenesis and metastasis of liver cancer. Materials and Methods: The orthotopic liver tumor model using a metastatic liver cancer cell line MHCC97L labeled with luciferase gene was applied. SAC was given at day 7 after tumor implantation at 1mg/g/day, 2mg/g/day, or 1mg/g/day combined with low dose Cisplatin for 5 weeks. Tumor growth and metastasis were monitored by Xenogen in vivo imaging system. Hepatic stellate cell (HSC) activation and tumor-associated macrophage (TAM) in the tumor tissue were detected by D-SMA and ED1/ED2 staining. Tumor micro-vessel density (MVD) and apoptosis were also analyzed. In vitro functional tests including MTT assay, colony formation assay, cell cycle analysis and apoptosis analysis were performed. Results: The tumor growth was significantly inhibited by SAC combined with Cisplatin treatment at different time points accompanied by lower incidence of lung metastasis compared with other groups. The observation of Xenogen IVIS was confirmed by histopathological examination. The HSC activation by D-SMA staining in the liver tumors was suppressed by SAC and Cisplatin treatment accompanied with less TAM infiltration. Consistent with in vivo study, in vitro functional study also demonstrated that SAC not only induced cell cycle arrest and tumor cell apoptosis, but also significantly sensitized the anti-cancer effect of Cisplatin. Conclusion: SAC treatment significantly inhibited liver tumor growth and metastasis by induction of tumor cell apoptosis and together with sensitization of chemotherapy.