Artesunate induces G0/G1 cell cycle arrest and iron-mediated mitochondrial apoptosis in A431 human epidermoid carcinoma cells
Artesunate induces G0/G1 cell cycle arrest and iron-mediated mitochondrial apoptosis in A431 human epidermoid carcinoma cells
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青蒿琥酯诱导 A431 人表皮样癌细胞 G0/G1 细胞周期阻滞和铁介导的线粒体凋亡
DOI：
10.1097/cad.0b013e328350e8ac
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发表时间：
2012-07-01
影响因子：
2.3
通讯作者：
Zhou, Deshan
中科院分区：
文献类型：
--
作者：
Jiang, Zhongyong;Chai, Jin;Zhou, Deshan
青蒿琥酯（ART）的抗癌作用已得到充分证明。然而，它对皮肤癌的潜力尚未被探索。本文报道了60 μ mol/l ART有效抑制A431（人表皮样癌细胞）的生长，但不抑制HaCaT（正常人角质形成细胞）的生长。结果显示ART通过下调细胞周期蛋白A1、细胞周期蛋白B、细胞周期蛋白D1、Cdk 2、Cdk 4和Cdk 6的表达，使细胞周期阻滞于G 0/G1期。这与p21和p27的上调有关。5-溴脱氧尿苷掺入试验也表明，ART治疗减少DNA合成的时间依赖性的方式。此外，ART诱导线粒体凋亡，证明了膜联蛋白V/碘化丙啶染色和蛋白质印迹分析。有趣的是，ART诱导的细胞凋亡在缺铁条件下减少，但在铁过载条件下增强。总之，这些发现证明了ART通过诱导G 0/G1细胞周期停滞和铁介导的线粒体凋亡治疗皮肤癌的潜力，并支持在其他测试系统中的进一步研究。抗癌药物23：606-613（C）2012年沃尔特斯·克鲁沃健康打破垂直酒吧利平科特威廉姆斯&威尔金斯。
The anticancer effects of artesunate (ART) have been well documented. However, its potential against skin cancer has not been explored yet. Herein we reported that 60 mu mol/l ART effectively inhibited A431 (human epidermoid carcinoma cells) growth but not that of HaCaT (normal human keratinocyte cells). Our results revealed that ART induced cell cycle arrest at G0/G1 phase through the downregulation of cyclin A1, cyclin B, cyclin D1, Cdk2, Cdk4, and Cdk6. This correlated with the upregulation of p21 and p27. The 5-bromodeoxyuridine incorporation assay also indicated that ART treatment reduced DNA synthesis in a time-dependent manner. Furthermore, ART induced mitochondrial apoptosis, as evidenced by annexin V/propidium iodide staining and western blot analysis. Interestingly, ART-induced apoptosis diminished under iron-deficient conditions but intensified under iron-overload conditions. Taken together, these findings demonstrated the potential of ART in treating skin cancer through the induction of G0/G1 cell cycle arrest and iron-mediated mitochondrial apoptosis and supported further investigations in other test systems. Anti-Cancer Drugs 23:606-613 (C) 2012 Wolters Kluwer Health broken vertical bar Lippincott Williams & Wilkins.