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Background  Crude extracts ofSelaginellatamariscina    , an oriental medicinal herb, have been evidenced to treat several human diseases. This study investigated the mechanisms by whichSelaginellatamariscinainhibits the invasiveness of human oral squamous-cell carcinoma (OSCC) HSC-3 cells.    Methodology/Principal Findings  Herein, we demonstrate thatSelaginellatamariscinaattenuated HSC-3 cell migration and invasion in a dose-dependent manner. The anti-metastatic activities ofSelaginellatamariscinaoccurred at least partially because of the down-regulation of matrix metalloproteinases (MMP)-2 and MMP-9 gelatinase activity and the down-regulation of protein expression. The expression and function of both MMP-2 and MMP-9 were regulated bySelaginellatamariscinaat a transcriptional level, as shown by quantitative real-time PCR and reporter assays. Chromatin immunoprecipitation (ChIP) data further indicated that binding of the cAMP response element-binding (CREB) protein and activating protein-1 (AP-1) to the MMP-2 promoter diminished at the highest dosage level ofSelaginellatamariscina    . The DNA-binding activity of specificity protein 1 (SP-1) to the MMP-9 promoter was also suppressed at the same concentration.Selaginellatamariscinadid not affect the mitogen-activated protein kinase signaling pathway, but did inhibit the effects of gelatinase by reducing the activation of serine–threonine kinase Akt.    Conclusions  These results demonstrate thatSelaginellatamariscinamay be a potent adjuvant therapeutic agent in the prevention of oral cancer.

Selaginella tamariscina Attenuates Metastasis via Akt Pathways in Oral Cancer Cells