Inhibition of tumor metastasis by sodium caffeate and its effect on angiogenesis

Objective: Sodium caffeate (SC), the sodium salt of caffeic acid, was synthesized in our laboratory. We studied the antimetastatic effect induced by SC and its inhibition of tumor angiogenesis using various in vitro and in vivo metastasis assays. Methods: The in vivo inhibitory effect of SC on metastasis and angiogenesis was examined in the Lewis lung carcinoma pulmonary metastasis model and chicken chorioallantoic membrane ( CAM) model, respectively. MTT assay and flow cytometry were used to measure the inhibition by SC of the proliferation of transformed human umbilical vein endothelial cells (ECV304) and the apoptosis induced by SC in ECV304 cells, respectively. A cell attachment assay was used to evaluate inhibition by SC of the adhesion activity of human high metastatic giant cell carcinoma of the lung ( PG) cells. A cell invasion assay was used to evaluate the effect of SC on the ability of PG cells to cross tissue barriers. Inhibition by SC of gelatinase secretion in PG cells was determined by zymography. Results: In vivo results showed that SC (1 g/kg i.p. for 14 days) inhibited pulmonary metastasis at a rate of 55%. There were no differences in animal weights among the groups. The angiogenesis of CAM was inhibited by SC (200 Ig/egg) at a rate of 70%. In vitro studies showed that SC inhibited the proliferation of ECV304 cells by inducing apoptosis. SC also reduced the adhesion and invasion ability of PG cells and inhibited the secretion of MMP-2 and MMP-9 in PG cells. Conclusion: SC might be a potential antimetastatic agent with an antiangiogenetic effect. Copyright (C) 2004 S. Karger AG, Basel.