Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Departments of Ophthalmology, Cathay General Hospital Sijhih Branch, New Taipei City, Taiwan.
Environ Toxicol. 2019 Mar;34(3):312-318. doi: 10.1002/tox.22686. Epub 2018 Nov 30.
Kaempferol is a flavonoid with anticancer and anti-metastasis activity in different cancer-cell lines. However, the underlying mechanisms by which kaempferol acts on human retinal pigment epithelial (ARPE-19) cells remain unclear. In this study, we demonstrated that kaempferol inhibited migration and invasion in ARPE-19 cells at non-toxic dosages. We discovered that kaempferol obviously reduced the enzyme activity and protein expression of matrix metalloproteinase-2 by increasing the phosphorylated levels of extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathways. Additionally, ERK1/2-specific inhibitor PD98059 significantly reversed kaempferol's inhibitory effects on migration and expression of MMP-2 in ARPE-19 cells. Overall, our results are the first to demonstrate that kaempferol is capable of inhibiting cell migration by targeting ERK1/2 signaling in human retinal pigment epithelial cells.
山奈酚是一种具有抗癌和抗转移活性的类黄酮,在不同的癌细胞系中都有表现。然而,山奈酚对人视网膜色素上皮(ARPE-19)细胞作用的潜在机制尚不清楚。在这项研究中,我们证明了山奈酚在非毒性剂量下抑制了 ARPE-19 细胞的迁移和侵袭。我们发现山奈酚通过增加细胞外信号调节激酶 1/2(ERK1/2)信号通路的磷酸化水平,明显降低了基质金属蛋白酶-2 的酶活性和蛋白表达。此外,ERK1/2 特异性抑制剂 PD98059 显著逆转了山奈酚对 ARPE-19 细胞迁移和 MMP-2 表达的抑制作用。总的来说,我们的研究结果首次证明,山奈酚通过靶向人视网膜色素上皮细胞中的 ERK1/2 信号通路,能够抑制细胞迁移。