Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
PLoS One. 2013 Jun 14;8(6):e68035. doi: 10.1371/journal.pone.0068035. Print 2013.
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.
These results demonstrate that Selaginellatamariscina may be a potent adjuvant therapeutic agent in the prevention of oral cancer.
东方草药卷柏的粗提取物已被证明可治疗多种人类疾病。本研究探讨了卷柏抑制人口腔鳞状细胞癌（OSCC）HSC-3 细胞侵袭的机制。
方法/主要发现：本文证明，卷柏以剂量依赖的方式减弱 HSC-3 细胞的迁移和侵袭。卷柏的抗转移活性至少部分是由于基质金属蛋白酶（MMP）-2 和 MMP-9 明胶酶活性的下调和蛋白表达的下调。MMP-2 和 MMP-9 的表达和功能均受卷柏在转录水平的调节，定量实时 PCR 和报告基因检测结果表明。染色质免疫沉淀（ChIP）数据进一步表明，在卷柏的最高剂量水平下，cAMP 反应元件结合（CREB）蛋白和激活蛋白-1（AP-1）与 MMP-2 启动子的结合减少。在相同浓度下，特异性蛋白 1（SP-1）与 MMP-9 启动子的 DNA 结合活性也受到抑制。卷柏不影响丝裂原活化蛋白激酶信号通路，但通过减少丝氨酸苏氨酸激酶 Akt 的激活来抑制明胶酶的作用。
这些结果表明，卷柏可能是预防口腔癌的有效辅助治疗剂。
