Dental Hospital, Jilin University, Changchun 130041, China.
Molecules. 2013 Jan 24;18(2):1418-33. doi: 10.3390/molecules18021418.
Despite the availability of several therapeutic options, a safer and more effective modality is urgently needed for treatment of bladder cancer. Costunolide, a member of sesquiterpene lactone family, possesses potent anticancer properties. In this study, for the first time we investigated the effects of costunolide on the cell viability and apoptosis in human bladder cancer T24 cells. Treatment of T24 cells with costunolide resulted in a dose-dependent inhibition of cell viability and induction of apoptosis which was associated with the generation of ROS and disruption of mitochondrial membrane potential (Δψm). These effects were significantly blocked when the cells were pretreated with N-acetyl- cysteine (NAC), a specific ROS inhibitor. Exposure of T24 cells to costunolide was also associated with increased expression of Bax, down-regulation of Bcl-2, survivin and significant activation of caspase-3, and its downstream target PARP. These findings provide the rationale for further in vivo and clinical investigation of costunolide against human bladder cancer.
尽管有几种治疗选择，但对于膀胱癌的治疗，迫切需要更安全、更有效的方法。千里光内酯是倍半萜内酯家族的一员，具有很强的抗癌特性。在这项研究中，我们首次研究了千里光内酯对人膀胱癌 T24 细胞活力和细胞凋亡的影响。用千里光内酯处理 T24 细胞，可导致细胞活力呈剂量依赖性抑制，并诱导细胞凋亡，这与 ROS 的产生和线粒体膜电位（Δψm）的破坏有关。当细胞用 N-乙酰半胱氨酸（NAC）预处理时，这些作用被显著阻断，NAC 是一种特定的 ROS 抑制剂。暴露于千里光内酯的 T24 细胞也与 Bax 表达增加、Bcl-2、存活素下调以及 caspase-3 及其下游靶标 PARP 的显著激活有关。这些发现为进一步对人膀胱癌进行体内和临床研究千里光内酯提供了依据。
