Phyllanthus urinaria suppresses human osteosarcoma cell invasion and migration by transcriptionally inhibiting u-PA via ERK and Akt signaling pathways.

Phyllanthus urinaria is widely used as anti-inflammatory, antiviral, antibacterial, and anti-hepatotoxic medicines in almost every tropical country. However, scientific evidence supporting its use in cancer metastasis is limited, particularly osteosarcoma. We investigated the effect of P. urinaria extract (PUE) on cell viability, invasion, and migration in the human osteosarcoma Saos-2 cell line, and looked at the impact of PUE on several relevant proteases and signaling pathways. This study demonstrates that PUE, at a range of concentrations (from 0 to 100 μg/ml), concentration-dependently inhibited the migration/invasion capacities of Saos-2 without cytotoxic effects. Zymographic and western blot analyses revealed that PUE inhibited the urokinase-type plasminogen activator (u-PA) and matrix metalloproteinase-2 (MMP-2) enzyme activity, as well as protein expression. Western blot analysis also showed that PUE inhibits phosphorylation of ERK1/2 and Akt. Testing of mRNA level, quantitative real-time PCR, and promoter assays evaluated the inhibitory effects of PUE on u-PA expression in Saos-2 cells. The chromatin immunoprecipitation (ChIP) assay was reactive to the transcription protein SP-1, which was inhibited by PUE. In conclusion, PUE suppresses human osteosarcoma Saos-2 cell invasion and migration by transcriptionally inhibiting u-PA via ERK and Akt signaling pathways. Therefore, PUE produces anti-metastatic activity in Saos-2 cells.

Lu KH ，Yang HW ，Su CW ，Lue KH ，Yang SF ，Hsieh YS ... -  《-》

Kaempferol suppresses cell metastasis via inhibition of the ERK-p38-JNK and AP-1 signaling pathways in U-2 OS human osteosarcoma cells.

Chen HJ ，Lin CM ，Lee CY ，Shih NC ，Peng SF ，Tsuzuki M ，Amagaya S ，Huang WW ，Yang JS ... -  《-》

Selaginella tamariscina (Beauv.) possesses antimetastatic effects on human osteosarcoma cells by decreasing MMP-2 and MMP-9 secretions via p38 and Akt signaling pathways.

Selaginella tamariscina is a traditional medicinal plant for treatment of some advanced cancers in the Orient. However, the effect of S. tamariscina on metastasis of osteosarcoma and the underlying mechanism remain unclear. We tested the hypothesis that S. tamariscina suppresses cellular motility, invasion and migration and also investigated its signaling pathways. This study demonstrates that S. tamariscina, at a range of concentrations (from 0 to 50 μg/mL), concentration-dependently inhibited the migration/invasion capacities of three osteosarcoma cell lines without cytotoxic effects. Zymographic and western blot analyses revealed that S. tamariscina inhibited the matrix metalloproteinase (MMP)-2 and MMP-9 enzyme activity, as well as protein expression. Western blot analysis also showed that S. tamariscina inhibits phosphorylation of p38 and Akt. Furthermore, SB203580 (p38 inhibitor) and LY294002 (PI3K inhibitor) showed the similar effects as S. tamariscina in U2OS cells. In conclusion, S. tamariscina possesses an antimetastatic activity in osteosarcoma cells by down-regulating MMP-2 and MMP-9 secretions and increasing TIMP-1 and TIMP-2 expressions through p38 and Akt-dependent pathways. S. tamariscina may be a powerful candidate to develop a preventive agent for osteosarcoma metastasis.

Yang JS ，Lin CW ，Hsieh YS ，Cheng HL ，Lue KH ，Yang SF ，Lu KH ... -  《-》

Antimetastatic potentials of Phyllanthus urinaria L on A549 and Lewis lung carcinoma cells via repression of matrix-degrading proteases.

Tseng HH ，Chen PN ，Kuo WH ，Wang JW ，Chu SC ，Hsieh YS ... -  《-》

The novel synthesized 6-fluoro-(3-fluorophenyl)-4-(3-methoxyanilino)quinazoline (LJJ-10) compound exhibits anti-metastatic effects in human osteosarcoma U-2 OS cells through targeting insulin-like growth factor-I receptor.

Chen KT ，Hour MJ ，Tsai SC ，Chung JG ，Kuo SC ，Lu CC ，Chiu YJ ，Chuang YH ，Yang JS ... -  《-》