Antimetastatic Potentials of Phyllanthus urinaria L on A549 and Lewis Lung Carcinoma Cells via Repression of Matrix-Degrading Proteases

Abstract

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.