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Selaginellatamariscina attenuates metastasis via Akt pathways in oral cancer cells
Jia-Sin Yang1, Chiao-Wen Lin, Chung-Han Hsin
1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Background:
Crude extracts of Selaginellatamariscina, an oriental medicinal herb, have been evidenced to treat several human diseases. This study investigated the mechanisms by which Selaginellatamariscina inhibits the invasiveness of human oral squamous-cell carcinoma (OSCC) HSC-3 cells.
Methodology/Principal Findings:
Herein, we demonstrate that Selaginellatamariscina attenuated HSC-3 cell migration and invasion in a dose-dependent manner. The anti-metastatic activities of Selaginellatamariscina 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 Selaginellatamariscina 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 Selaginellatamariscina. The DNA-binding activity of specificity protein 1 (SP-1) to the MMP-9 promoter was also suppressed at the same concentration. Selaginellatamariscina 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 Selaginellatamariscina may be a potent adjuvant therapeutic agent in the prevention of oral cancer.
Insights
Selaginella tamariscina inhibits oral cancer cell invasion by down-regulating matrix metalloproteinases (MMP-2 and MMP-9). This oriental herb may serve as an adjuvant therapy to prevent oral cancer metastasis.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Selaginella tamariscina, an oriental medicinal herb, shows therapeutic potential for various diseases.
- Human oral squamous-cell carcinoma (OSCC) is a significant health concern.
- Investigating the anti-cancer mechanisms of S. tamariscina is crucial for developing new treatments.
Purpose of the Study:
- To elucidate the mechanisms by which Selaginella tamariscina inhibits the invasiveness of human oral squamous-cell carcinoma (OSCC) HSC-3 cells.
- To evaluate the anti-metastatic potential of S. tamariscina extracts.
Main Methods:
- Cell migration and invasion assays were performed.
- Matrix metalloproteinases (MMP)-2 and MMP-9 activity and expression were analyzed.
- Quantitative real-time PCR, reporter assays, and chromatin immunoprecipitation (ChIP) were utilized to assess transcriptional regulation.
- Western blotting and kinase activity assays were employed to study signaling pathways.
Main Results:
- Selaginella tamariscina dose-dependently inhibited HSC-3 cell migration and invasion.
- The herb downregulated the activity and expression of MMP-2 and MMP-9 at the transcriptional level.
- Inhibition involved decreased binding of transcription factors (CREB, AP-1, SP-1) to MMP promoters and reduced Akt activation.
Conclusions:
- Selaginella tamariscina exhibits potent anti-metastatic properties against oral cancer cells.
- The downregulation of MMP-2 and MMP-9 is a key mechanism of action.
- Selaginella tamariscina shows promise as an adjuvant therapeutic agent for oral cancer prevention.
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