Sodium caffeate induces endothelial cell apoptosis and inhibits VEGF expression in cancer cells.
OBJECTIVE
To investigate the induction of endothelial cell apoptosis and the suppression of VEGF expression in cancer cells by sodium caffeate (SCA).


METHODS
Apoptosis of transformed human umbilical vein endothelial cells (ECV304 cell line) was detected by flow cytometry, DNA electrophoresis assay and morphological assessment. Western blotting analysis was applied for determination of VEGF expression in cancer cells. Substrate degradation by type IV collagenase was measured by zymography. ELISA was used to detect the binding of type IV collagenase with relevant monoclonal antibody.


RESULTS
SCA induced ECV304 cell apoptosis in a time- and dose-dependent manner. After treatment with 100 and 250 microg X mL(-1) of SCA for 48 h, DNA laddering appeared. SCA treated cells showed strong blue fluorescence and distinct changes of nuclear morphology, such as pyknosis and the occurrence of apoptotic bodies. VEGF expression in hepatoma HepG-2 cells and prostate carcinoma DU145 cells was reduced after SCA treatment. The degradation activity of type IV collagenase including MMP-2 and MMP-9 secreted by giant cell pulmonary carcinoma PG cells was inhibited by SCA in a dose-dependent manner. SCA also reduced the binding of mAb 3D6, a relevant monoclonal antibody, to type IV collagenase.


CONCLUSIONS
SCA can induce endothelial cell apoptosis and inhibit VEGF expression as well as type IV collagenase activity in cancer cells. SCA might be active in modulating tumor angiogenesis and the microenvironment.
Xu
Feng
F
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Ou-Yang
Zhi-Gang
ZG
Zhang
Sheng-Hua
SH
Song
Dan-Qing
DQ
Shao
Rong-Guang
RG
Zhen
Yong-Su
YS
D017209:Apoptosis / Q000187:drug effects*; D002109:Caffeic Acids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D002109:Caffeic Acids; D042461:Vascular Endothelial Growth Factor A; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C040048:caffeic acid