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 microg/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.


CONCLUSIONS
SC might be a potential antimetastatic agent with an antiangiogenic effect.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing. andrewfxu@sina.com.cn
Feng
F
Xu
Danqing
D
Song
Yongsu
Y
Zhen
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002109:Caffeic Acids / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000975:Antioxidants; D002109:Caffeic Acids; D004791:Enzyme Inhibitors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C040048:caffeic acid