Shikonin induces apoptosis of HaCaT cells via the mitochondrial, Erk and Akt pathways.
Shikonin induces apoptosis of HaCaT cells via the mitochondrial, Erk and Akt pathways.
复制标题
紫草素通过线粒体、Erk 和 Akt 途径诱导 HaCaT 细胞凋亡
DOI：
10.3892/mmr.2016.4917
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发表时间：
2016-04
影响因子：
3.4
通讯作者：
Zheng Y
中科院分区：
文献类型：
--
作者：
Jing H;Sun W;Fan J;Zhang Y;Yang J;Jia J;Li J;Guo J;Luo S;Zheng Y
紫草素是传统中草药紫草的主要成分，具有抗菌、抗炎、抗肿瘤等多种生物学功能。本研究旨在探讨紫草素诱导HaCaT细胞凋亡的分子机制。紫草素以剂量和时间依赖的方式抑制HaCaT细胞的活力，并促进细胞周期停滞于G0/G1期和促进细胞凋亡。此外，紫草素处理降低了线粒体膜电位，诱导了活性氧的产生。免疫印迹分析结果显示，紫草素可剂量依赖性地激活HaCaT细胞caspase3的表达，下调B细胞淋巴瘤2(Bcl2)的表达，上调Bcl2相关的X蛋白和Bcl2同源拮抗剂Killer的表达。此外，紫草素还可降低细胞外信号调节激酶(ERK)和Akt的磷酸化。这些结果表明紫草素可能通过激活线粒体信号通路和失活Akt和Erk通路来诱导HaCaT细胞的凋亡，从而发挥其抗增殖作用。因此，本研究提示紫草素可能有潜力作为治疗皮肤病的治疗策略的组成部分。
Shikonin, which is a major ingredient of the traditional Chinese herb Lithospermum erythrorhizon, possesses various biological functions, including antimicrobial, anti-inflammatory, and antitumor activities. The present study aimed to determine the molecular mechanisms underlying the effects of shikonin on HaCaT cell apoptosis. Treatment with shikonin significantly inhibited the viability of HaCaT cells in a dose- and time-dependent manner, and promoted cell cycle arrest at G0/G1 phase and apoptosis. In addition, shikonin treatment reduced the mitochondrial membrane potential and induced reactive oxygen species generation. The results of a western blot analysis demonstrated that shikonin significantly activated caspase 3 expression, downregulated B-cell lymphoma 2 (Bcl-2) expression, and upregulated Bcl-2-associated X protein and Bcl-2 homologous antagonist killer expression in a dose-dependent manner in HaCaT cells. Furthermore, shikonin decreased extracellular signal-regulated kinase (Erk) and Akt phosphorylation. These results indicated that shikonin may exert its anti-proliferative effects by inducing apoptosis via activation of the mitochondrial signaling pathway and inactivation of the Akt and Erk pathways in HaCaT cells. Therefore, the present study suggested that shikonin may have potential as a component of therapeutic strategies for the treatment of skin diseases.