Andrographolide inhibits the adhesion of gastric cancer cells to endothelial cells by blocking E-selectin expression.
BACKGROUND
Andrographolide, an active component isolated from the Chinese official herbal Andrographis paniculata, has recently been reported to have anticancer activity. However the molecular mechanism responsible for its anticancer action has not been fully defined. In this study, we investigated the effect of andrographolide on the adhesion of gastric cancer cells to the activated endothelial cells and the expression of some cell adhesion molecules.


METHODS
Human endothelial cells were preincubated with andrographolide for 6 h and then incubated with the cytokine tumor necrosis factor for 4 h. Endothelial surface expression of E-selectin was evaluated by flow cytometry, immunostaining and ELISA. Further, we investigated E-selectin mRNA expression by RT-PCR. Surface expression of sialyl Lewis(X) of three gastric cancer cell lines (SGC7901, MGC803, BGC823) and a normal gastric epithelial cell line GES-1 was evaluated by flow cytometry and immunostaining. Adherence of CFSE-labeled gastric cancer cells and GES-1 cells to endothelial cell monolayers was then determined.


RESULTS
Andrographolide significantly reduced E-selectin expression of activated endothelial cells, and inhibited the E-selectin expression on mRNA level. Three gastric cancer cell lines expressed high levels of sialyl Lewis(X), whereas GES-1 did not. Andrographolide also significantly decreased gastric cancer cells adherence to stimulated endothelial cells. The inhibition of E-selectin expression corresponded to the reduction of tumor cell adherence. The effects of andrographolide on tumor adhesion were almost nullified by pre-incubation with E-selectin and sialyl Lewis(X) antibody.


CONCLUSIONS
These findings demonstrate that andrographolide suppresses the adhesion of gastric cancer cells which express high level sialyl Lewis(X) to human vascular endothelial cells by blocking E-selectin expression and, thus, may represent a candidate therapeutic agent for cancer.
Jiang
Cheng-Gang
CG
Department of Oncology, The First Affiliated Hospital, Shenyang, Liaoning Province, China.
Li
Jia-Bin
JB
Liu
Fu-Rong
FR
Wu
Tao
T
Yu
Miao
M
Xu
Hui-Mian
HM
D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology*; D019040:E-Selectin / Q000096:biosynthesis* / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009844:Oligosaccharides / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000080506:Sialyl Lewis X Antigen; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D004224:Diterpenes; D019040:E-Selectin; D009844:Oligosaccharides; D012333:RNA, Messenger; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha; C030419:andrographolide