Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
Mol Nutr Food Res. 2011 May;55 Suppl 1:S103-16. doi: 10.1002/mnfr.201000336. Epub 2010 Nov 18.
Acteoside, an active phenylethanoid glycoside found in bitter tea and many medicinal plants, displays chemopreventive properties. The aim of our study was to determine the effect of acteoside on tumor invasion and migration; the possible mechanisms involved in this inhibition were investigated in human fibrosarcoma HT-1080 cells.
We employed invasion, migration and gelatin zymography assays to characterize the effect of acteoside on HT-1080 cells. Transient transfection assays were performed to investigate gene promoter activities, and immunoblot analysis to study its molecular mechanisms of action. We found that acteoside suppresses phorbol-12-myristate-13-acetate (PMA)-enhanced matrix metalloproteinase-9 (MMP-9) expression at the protein, mRNA, and transcriptional levels through the suppression of NF-κB activation. In addition, acteoside repressed the PMA-induced phosphorylation of ERK1/2 (ERK, extracellular regulated kinase) and JNK1/2. Further, we found that acteoside decreased the PMA-induced influx of Ca(2+) and repressed PMA-induced calmodulin-dependent protein kinase (CaMK) phosphorylation. Furthermore, treatment with BAPTA/AM, W7, or capsazepine markedly decreased PMA-induced MMP-9 secretion and cell migration, as well as ERK and JNK/NF-κB activation.
Acteoside inhibited PMA-induced invasion and migration of human fibrosarcoma cells via Ca(2+) -dependent CaMK/ERK and JNK/NF-κB-signaling pathways. Acteoside therefore has the potential to be a potent anticancer agent in therapeutic strategies for fibrosarcoma metastasis.
咖啡酸苯乙酯，一种存在于苦茶和许多药用植物中的活性苯乙醇苷，具有化学预防特性。本研究的目的是确定咖啡酸苯乙酯对肿瘤侵袭和迁移的影响；在人纤维肉瘤 HT-1080 细胞中研究了这种抑制作用涉及的可能机制。
我们采用侵袭、迁移和明胶酶谱分析来描述咖啡酸苯乙酯对 HT-1080 细胞的影响。进行瞬时转染实验以研究基因启动子活性，并用免疫印迹分析研究其作用机制。我们发现咖啡酸苯乙酯通过抑制 NF-κB 激活，抑制 PMA 增强的基质金属蛋白酶-9（MMP-9）表达，在蛋白质、mRNA 和转录水平上。此外，咖啡酸苯乙酯抑制了 PMA 诱导的 ERK1/2（细胞外调节激酶）和 JNK1/2 的磷酸化。此外，我们发现咖啡酸苯乙酯降低了 PMA 诱导的 Ca2+内流，并抑制了 PMA 诱导的钙调蛋白依赖性蛋白激酶（CaMK）磷酸化。此外，用 BAPTA/AM、W7 或辣椒素处理可显著降低 PMA 诱导的 MMP-9 分泌和细胞迁移，以及 ERK 和 JNK/NF-κB 的激活。
咖啡酸苯乙酯通过 Ca2+依赖性 CaMK/ERK 和 JNK/NF-κB 信号通路抑制 PMA 诱导的人纤维肉瘤细胞侵袭和迁移。因此，咖啡酸苯乙酯有可能成为纤维肉瘤转移治疗策略中的一种有效的抗癌药物。
