Src kinase is a direct target of apigenin against UVB-induced skin inflammation
Src kinase is a direct target of apigenin against UVB-induced skin inflammation
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DOI：
10.1093/carcin/bgs358
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发表时间：
2013-02-01
期刊：
影响因子：
4.7
通讯作者：
Lee, Hyong Joo
中科院分区：
文献类型：
--
作者：
Byun, Sanguine;Park, Jiman;Lee, Hyong Joo
芹菜素是一种富含于包括欧芹和洋葱在内的多种蔬菜和水果中的类黄酮类化合物，已有报道具有抗癌作用。然而，芹菜素的直接分子靶点及其对紫外线(UV)诱导的皮肤炎症的化学预防作用尚不完全清楚。在此，我们在JB6P+细胞系和SKH-1无毛小鼠模型上研究了芹菜素的抗炎作用及其相关机制。芹菜素可抑制UVB诱导的炎症和癌症关键介质环氧合酶-2(COX-2)的表达，并恢复JB6P+细胞上游刺激因子水平。免疫印迹和蛋白激酶检测结果表明，芹菜素可抑制Src的活性，进而抑制UVB诱导的表皮生长因子受体、丝裂原活化蛋白激酶和Akt信号的磷酸化。在HaCaT人角质形成细胞中，也证实了芹菜素对UVB诱导的信号转导的抑制作用。此外，体外下拉实验表明，芹菜素以三磷酸腺苷竞争的方式与Src结合。结果在体皮肤模型显示，芹菜素显著抑制中波紫外线诱导的无毛小鼠耳肿胀的形成、COX-2的表达和Src激酶的活性。总之，这些发现表明，芹菜素主要通过靶向Src而对UVB诱导的皮肤炎起到有效的化学预防作用。
Apigenin, a flavonoid abundant in various vegetables and fruits, including parsley and onions, has been reported to possess anti-carcinogenic effects. However, the direct molecular target of apigenin and its chemopreventive effect on ultraviolet (UV)-induced skin inflammation are not understood fully. Herein, we examined the anti-inflammatory effect of apigenin and its associated mechanisms in JB6 P+ cell line and SKH-1 hairless mouse model. Apigenin inhibited UVB-induced cyclooxygenase-2 (COX-2) expression, which is a well-known key mediator of inflammation and cancer, and restored the upstream stimulatory factor level in JB6 P+ cells. Immunoblot and kinase assay data demonstrate that Src activity was attenuated by apigenin, and this led to subsequent inhibition of UVB-induced phosphorylation of epidermal growth factor receptor, mitogen-activated protein kinases and Akt signaling. Inhibitory effects of apigenin on UVB-induced signaling were also confirmed in HaCaT human keratinocytes. In addition, in vitro pull-down assays revealed that apigenin binds Src in an adenosine triphosphate-competitive manner. Results using in vivo skin model indicate apigenin significantly inhibits UVB-induced ear edema development, COX-2 expression and Src kinase activity in SKH-1 hairless mice. Collectively, these findings suggest that apigenin exerts potent chemopreventive activity against UVB-induced skin inflammation primarily by targeting Src.