Tumor metastasis is the most important cause of
cancer death and various treatment strategies have targeted at preventing the occurrence of
metastasis. Phyllanthus urinaria L is a popular
folk medicine and has several proven
biological properties, including
antioxidant, antihypertension, and anti-inflammatory. This study provides molecular evidence associated with the antimetastatic effects of P urinaria L extracts (PUE), which contained
polyphenols including
gallic acid,
methyl gallate,
epicatechin,
epigallocatechin-3-gallate,
gallocatechin-3-gallate,
rutin,
epicatechin-3-gallate, and
naringin, by showing a marked inhibition on the invasion (P < .001) and migration (P < .001) of highly metastatic A549 and
Lewis lung carcinoma (LLC) cells. To further investigate the precise involvement of PUE in
tumor metastasis, A549 and LLC cells were treated with PUE at various concentrations and results from zymography and Western blotting showed that a PUE treatment may decrease the expressions of
matrix metalloproteinase-2 (
MMP-2; P < .001), MMP-9 (P < .001),
urokinase plasminogen activator (P < .001), and their endogenous inhibitors, that is,
tissue inhibitor of metalloproteinase-2 and
plasminogen activator inhibitor-1, in a concentration-dependent manner. Reverse transcription-polymerase chain reaction and MMP-2 promoter
luciferase analysis (P < .001) revealed that PUE inhibits the transcription of MMP-2
mRNA. PUE also exerted an inhibitory effect on the
DNA-binding activity and the nuclear translocation of NF-κB and
AP-1. Furthermore, the inhibitory effects of PUE on the
metastasis and growth of LLC cells in vivo were proven. These results indicate that PUE could be applied to be a potential antimetastatic agent.