Suppression of PMA-induced tumor cell invasion and metastasis by aqueous extract isolated from Prunella vulgaris via the inhibition of NF-kappaB-dependent MMP-9 expression.

Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. In this study, we examined the inhibitory effects of tumor cell migration and invasion by aqueous extract isolated from Prunella vulgaris (PVAE) using in vitro and in vivo assays. PVAE reduced PMA-induced activation of MMP-9 and further inhibited cell invasion and migration. PVAE suppressed PMA-enhanced expression of MMP-9 protein, mRNA and transcription activity levels through suppression of NF-kappaB activation without changing the tissue inhibitor of metalloproteinase level. PVAE inhibited PMA-induced NF-kappaB nuclear translocation, which is upstream of PMA-induced MMP-9 expression and invasion. Furthermore, pretreatment with NF-kappaB activation inhibitor inhibited the PMA-induced MMP-9 expression and activity. PVAE repressed the PMA-induced phosphorylation of ERK1/2, which is upstream signaling molecules in MMP-9 expression. We confirmed that the inhibitory effect of PVAE on lung metastasis and tumor cell growth using B16-F10 melanoma cells or B16-F1 melanoma cells in C57BL/6 mice. The oral administrations of PVAE reduced the lung metastasis and tumor cell growth by B16-F10 or B16-F1 melanoma cells. These results suggested that the anti-metastatic effect of PVAE is mediated through the suppression of MMP-9 expression by the inhibition of NF-kappaB via ERK1/2 signaling pathway as well as MMP-9 activity.

Choi JH ，Han EH ，Hwang YP ，Choi JM ，Choi CY ，Chung YC ，Seo JK ，Jeong HG ... -  《-》

Kalopanaxsaponin A inhibits PMA-induced invasion by reducing matrix metalloproteinase-9 via PI3K/Akt- and PKCdelta-mediated signaling in MCF-7 human breast cancer cells.

Park SK ，Hwang YS ，Park KK ，Park HJ ，Seo JY ，Chung WY ... -  《-》

Saponins derived from the roots of Platycodon grandiflorum inhibit HT-1080 cell invasion and MMPs activities: regulation of NF-kappaB activation via ROS signal pathway.

Lee KJ ，Hwang SJ ，Choi JH ，Jeong HG ... -  《-》

Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by piperine via the inhibition of PKCα/ERK1/2-dependent matrix metalloproteinase-9 expression.

Piperine is a major component of black pepper, Piper nigrum Linn, used widely in traditional medicine. Several previous studies reported that piperine possesses various beneficial biological activities including antioxidant, anti-tumor and anti-inflammation properties. In the present study, we investigated the inhibitory effects of piperine on tumor invasion and migration and the possible mechanisms involved using human fibrosarcoma HT-1080 cells. We found that piperine suppresses PMA-enhanced matrix metalloproteinase-9 (MMP-9) expression at the protein, mRNA, and transcriptional levels through the suppression of NF-κB and AP-1 activation without changing the level of tissue inhibitor of metalloproteinase (TIMP)-1. Piperine also inhibits PMA-enhanced membrane-type 1 MMP expression without changing the level of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Piperine inhibited PMA-induced NF-κB and c-Jun nuclear translocation, which are upstream of PMA-induced MMP-9 expression and invasion. Furthermore, piperine strongly repressed the PMA-induced phosphorylation of ERK, which are dependent on the PKCα pathway. In conclusion, we demonstrated that the anti-invasive effects of piperine may occur through inhibition of PKCα and ERK phosphorylation and reduction of NF-κB and AP-1 activation, leading to down-regulation of MMP-9 expression. Thus, piperine has potential as a potent anti-cancer drug in therapeutic strategies for fibrosarcoma metastasis.

Hwang YP ，Yun HJ ，Kim HG ，Han EH ，Choi JH ，Chung YC ，Jeong HG ... -  《-》

Inhibition of invasion and experimental metastasis of murine melanoma cells by Ipomoea obscura (L.) is mediated through the down-regulation of inflammatory mediators and matrix-metalloproteinases.

Hamsa TP ，Kuttan G 《-》