Deoxyelephantopin suppresses lung metastasis of B16 melanoma in mice

Elephantopus scaber L. (Asteraceae) is a traditional herbal medicine claimed for anti-cancer effects. We evaluated the in vitro and in vivo efficacy of a major sesquiterpene lactone constituent of E. scaber, deoxyelephantopin (DET), for its anti-B16 melanoma cell activity and the underlying molecular mechanism. Our data show that DET could induce cell cycle arrest at G2/M phase at 5 mM, with the decrease of cyclins A, B1, and D1 protein expression. When increased DET concentration to 8 mM, apoptotic hallmarks PARP and caspase 3 were activated in a time-dependent manner. DET also inhibited B16 cell migration accompanied with inhibiting of MMP-9 activity. A non-invasive real-time in vivo imaging system to monitor the melanoma cell growth and metastasis in mice is created in this study. The stable B16 melanoma cell clone carrying COX-2 promoter driven-luciferase gene was established and used to comparative study of the efficacy of DET and a chemotherapeutic drug cisplatin in C57BL/6J mice. We observed that Pre-DET10 (10mg/kg BW), and cisplatin (CP, 2mg/kg BW) have similar profound effect on inhibiting lung metastasis of B16 melanoma and increase of median survival rate in tested mice (tumor control: 33 days, pre-DET10: 43 days, CP2: 43 days). Notably, Pre-DET10 treatment has little or no side-effects compared to cisplatin treatment in mice. This report presents the novel pharmacological effect of DET which may be worthy for further development into an agent against skin melanoma.