Inhibitory effects of evodiamine on in vitro invasion and experimental lung metastasis of murine colon cancer cells

We have previously reported that evodiamine had a marked inhibitory activit y on tumor cell migration in vitro. To extend our study, the effects of evo diamine on invasion, growth, and metastatic development of colon 26-L5 cell s were examined here. Evodiamine inhibited the invasion of tumor cells into Matrigel in a concentration-dependent manner, and achieved 70% inhibition at 10 mug/ml. Treatment of tumor cells with evodiamine for 24 h showed litt le effect on tumor growth at concentrations of less than 10 mug/ml, whereas an over 48-h treatment resulted in a concentration- and time-dependent inh ibition. Pretreatment of tumor cells with 10 mug/ml evodiamine before inocu lation into mice caused 70% reduction in their lung metastasis formation. W hen evodiamine at 10 mg/kg was administered into mice from the 6th day afte r tumor inoculation, the number of tumor nodules in lungs was decreased by 48% as compared to control. The inhibition rate was equivalent to that prod uced by cisplatin, a potent anti-cancer drug. Evodiamine did not affect the body weight of mice in the experimental period, whereas cisplatin caused s erious weight loss. These results suggest that evodiamine may be regarded a s a promising agent in tumor metastasis therapy.