China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, People's Republic of China.
J Nat Prod. 2010 Jun 25;73(6):1058-63. doi: 10.1021/np9008199.
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 (DeltaPsi(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/WAF1-dependent manner 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.
冬凌草甲素（1）是从植物冬凌草中分离得到的一种活性成分，具有抗肿瘤作用。本研究首次探讨了冬凌草甲素（1）诱导人喉癌细胞（HEp-2）生长抑制的机制，该细胞 p53 功能缺失。化合物 1 通过增加 Bax/Bcl-2 比值、降低线粒体膜电位（DeltaPsi(m)）和显著增加凋亡诱导因子（AIF）和细胞色素 c ，触发线粒体凋亡途径。在 HEp-2 细胞中抑制 caspase-9 并不能保护细胞免受 1 诱导的凋亡，也没有检测到裂解的 caspase-9，表明凋亡是通过 caspase-9 非依赖性途径发生的。结果还表明，在 HEp-2 细胞中，1 诱导的 G2/M 期阻滞和凋亡是通过 p53 非依赖性但 p21/WAF1 依赖性方式发生的。此外，还发现活性氧（ROS）的产生是 1 诱导生长抑制的关键介质。综上所述，这些结果表明冬凌草甲素（1）可能是治疗喉鳞状细胞癌的有效药物。
