Induction of G2/M Phase Arrest and Apoptosis by Oridonin in Human Laryngeal Carcinoma Cells
Induction of G2/M Phase Arrest and Apoptosis by Oridonin in Human Laryngeal Carcinoma Cells
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DOI：
10.1021/np9008199
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发表时间：
2010-06-01
影响因子：
5.1
通讯作者：
Ikejima, Takashi
中科院分区：
文献类型：
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作者：
Kang, Ning;Zhang, Jing-Hai;Ikejima, Takashi
oriidonin(1)是一种从植物Rabdosia rubescens中分离出来的活性成分，据报道具有抗肿瘤作用。在这项研究中，机制涉及1诱导的生长抑制，包括凋亡和G(2)/M期阻滞，在人喉癌HEp-2细胞缺乏功能性p53。第一次被调查。化合物1触发线粒体凋亡通路，Bax/Bcl-2比值升高，线粒体膜电位（δ Psi(m)）降低，凋亡诱导因子（AIF）和细胞色素c大幅增加。HEp-2细胞中caspase-9的抑制作用不能保护细胞免受1诱导的凋亡，且未检测到裂解的caspase-9，表明凋亡是通过caspase-9独立通路发生的。结果还表明，在HEp-2细胞中，1介导的G(2)/M期阻滞和凋亡是通过p53独立而p21/ wafi依赖的途径发生的。此外，发现活性氧（ROS）的产生是1诱导的生长抑制的关键介质。综上所述，这些结果表明，oriidonin(1)是治疗喉部鳞状细胞癌的潜在有效药物。
Oridonin (1), an active component isolated from the plant Rabdosia rubescens, has been reported to exhibit antitumor effects. In this study, the mechanism involved in 1-induced growth inhibition, including apoptosis and G(2)/M phase arrest, in human laryngeal carcinoma HEp-2 cells deficient in functional p53. was investigated for the first time. Compound 1 triggered the mitochondrial apoptotic pathway, as indicated by increased Bax/Bcl-2 ratios, reduction of mitochondrial membrane potential (Delta Psi(m)), and substantial increase in apoptosis-inducing factor (AIF) and cytochrome c. Inhibition of caspase-9 in HEp-2 cells did not protect the cells from 1-induced apoptosis, and cleaved caspase-9 was not detected, indicating that apoptosis occurred via a caspase-9-independent pathway. The results also suggested that G(2)/M phase arrest and apoptosis mediated by 1 occurred via a p53-independent but in a p21/WAFI-dependent manlier in HEp-2 cells. In addition, the generation of reactive oxygen species (ROS) was found to be a critical mediator in growth inhibition induced by 1. Taken together, the results indicate that oridonin (1) is a potentially effective agent for the treatment of laryngeal squamous cell carcinoma.