Abstract
BackgroundCrude extracts of Selaginella tamariscina , an oriental medicinal herb, have been evidenced to treat several human diseases. This study investigated the mechanisms by which Selaginella tamariscina inhibits the invasiveness of human oral squamous-cell carcinoma (OSCC) HSC-3 cells.Methodology/Principal FindingsHerein, we demonstrate that Selaginella tamariscina attenuated HSC-3 cell migration and invasion in a dose-dependent manner. The anti-metastatic activities of Selaginella tamariscina occurred 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 by Selaginella tamariscina at 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 of Selaginella tamariscina . The DNA-binding activity of specificity protein 1 (SP-1) to the MMP-9 promoter was also suppressed at the same concentration. Selaginella tamariscina did 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.ConclusionsThese results demonstrate that Selaginella tamariscina may be a potent adjuvant therapeutic agent in the prevention of oral cancer.
Highlights
Head and neck squamous-cell carcinoma accounts for approximately 3% of all cancers in the United States, and oral squamous-cell carcinoma (OSCC) is the most common form of head and neck cancer [1]
Our results showed that Selaginella tamariscina halted oral cancer cell migration through the down-regulation of matrix metalloproteinases (MMP)-2 and MMP-9 expression and by decreasing DNA-binding activity to promoter elements
The results demonstrate that Selaginella tamariscina significantly reduced cell motility both time- and dose-dependently (p
Summary
Head and neck squamous-cell carcinoma accounts for approximately 3% of all cancers in the United States, and oral squamous-cell carcinoma (OSCC) is the most common form of head and neck cancer [1]. MMP-2, known as gelatinase A, is a 72-kDa protein expressed in most tissues and cells [6]. Elevated MMP-2 and MMP-9 expression have been observed in invasive and metastatic cases of human oral cancer [8,9,10]. This study investigated the mechanisms by which Selaginella tamariscina inhibits the invasiveness of human oral squamous-cell carcinoma (OSCC) HSC-3 cells. The anti-metastatic activities of Selaginella tamariscina occurred 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. Selaginella tamariscina did 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 that Selaginella tamariscina may be a potent adjuvant therapeutic agent in the prevention of oral cancer
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