Lin Chiao-Wen, Chou Ying-Erh, Chiou Hui-Ling, Chen Mu-Kuan, Yang Wei-En, Hsieh Ming-Ju, Yang Shun-Fa
Chung Shan Medical University, Institute of Oral Sciences , Taichung 40201 , Taiwan.
Expert Opin Ther Targets. 2014 Oct;18(10):1109-20. doi: 10.1517/14728222.2014.947962. Epub 2014 Aug 9.
Polyphenol compounds, present in a wide variety of natural plants, exhibit antioxidant and free radical scavenging ability and induce apoptosis in various cancer cells. However, the effect of pterostilbene on oral cancer cell metastasis has not been clarified.
The present study aimed to examine the anti-metastatic properties of pterostilbene in human oral squamous cell carcinoma (SCC)-9 cells.
In this study, pterostilbene treatment significantly inhibited migration/invasion capacities of SCC-9 cells in vitro. The results of zymography and western blotting revealed that the activities and protein levels of the MMP-2 and urokinase-type plasminogen activator (u-PA) was inhibited by pterostilbene. Western blot analysis also showed that pterostilbene inhibits the phosphorylation of Akt, extracellular signal-regulated kinase 1/2 and p38. Determinations of the mRNA levels, real-time polymerase chain reaction and promoter assays were conducted to evaluate the inhibitory effects of pterostilbene on MMP-2 and u-PA expression in SCC-9 cells. Such inhibitory effects were associated with the upregulation of tissue inhibitor of metalloproteinase-2, plasminogen activator inhibitor-1 and the downregulation of the transcription factors of NF-κB, SP-1 and CREB signaling pathways.
Pterostilbene may have potential use as a chemopreventive agent against oral cancer metastasis.
存在于多种天然植物中的多酚化合物具有抗氧化和清除自由基的能力,并能诱导多种癌细胞凋亡。然而,紫檀芪对口腔癌细胞转移的影响尚未阐明。
本研究旨在检测紫檀芪对人口腔鳞状细胞癌(SCC)-9细胞的抗转移特性。
在本研究中,紫檀芪处理显著抑制了SCC-9细胞在体外的迁移/侵袭能力。酶谱分析和蛋白质印迹结果显示,紫檀芪抑制了基质金属蛋白酶-2(MMP-2)和尿激酶型纤溶酶原激活剂(u-PA)的活性和蛋白水平。蛋白质印迹分析还表明,紫檀芪抑制了Akt、细胞外信号调节激酶1/2和p38的磷酸化。通过实时聚合酶链反应和启动子分析测定mRNA水平,以评估紫檀芪对SCC-9细胞中MMP-2和u-PA表达的抑制作用。这种抑制作用与金属蛋白酶组织抑制剂-2、纤溶酶原激活剂抑制剂-1的上调以及NF-κB、SP-1和CREB信号通路转录因子的下调有关。
紫檀芪可能具有作为预防口腔癌转移化学预防剂的潜在用途。