Powolny Anna A, Singh Shivendra V
Department of Pharmacology and Urology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Pharm Res. 2008 Sep;25(9):2171-80. doi: 10.1007/s11095-008-9533-3. Epub 2008 Jan 23.
To investigate the mechanism of human prostate cancer cell growth inhibition by plumbagin, a constituent of the widely used medicinal herb Plumbago zeylanica L.
Cell viability was determined by trypan blue dye exclusion assay. Apoptosis induction was assessed by analysis of cytoplasmic histone-associated DNA fragmentation. Cell cycle distribution and generation of reactive oxygen species (ROS) were determined by flow cytometry. The effect of plumbagin treatment on cellular redox status was determined by analysis of intracellular glutathione (GSH) levels and expression of genes involved in ROS metabolism.
Plumbagin treatment decreased viability of human prostate cancer cells (PC-3, LNCaP, and C4-2) irrespective of their androgen responsiveness or p53 status. Plumbagin-mediated decrease in cell viability correlated with apoptosis induction, which was accompanied by ROS generation and depletion of intracellular GSH levels. Pretreatment of cells with the antioxidant N-acetylcysteine inhibited plumbagin-mediated ROS generation and apoptosis. Plumbagin treatment also resulted in altered expression of genes responsible for ROS metabolism, including superoxide dismutase 2 (Mn-SOD).
The present study points towards an important role of ROS in plumbagin-induced apoptosis in human prostate cancer cells.
研究白花丹素（一种广泛使用的药用植物白花丹的成分）对人前列腺癌细胞生长抑制的机制。
通过台盼蓝拒染法测定细胞活力。通过分析细胞质组蛋白相关DNA片段化评估凋亡诱导情况。通过流式细胞术测定细胞周期分布和活性氧（ROS）的产生。通过分析细胞内谷胱甘肽（GSH）水平和参与ROS代谢的基因表达来确定白花丹素处理对细胞氧化还原状态的影响。
白花丹素处理降低了人前列腺癌细胞（PC-3、LNCaP和C4-2）的活力，无论其雄激素反应性或p53状态如何。白花丹素介导的细胞活力降低与凋亡诱导相关，凋亡诱导伴随着ROS的产生和细胞内GSH水平的消耗。用抗氧化剂N-乙酰半胱氨酸预处理细胞可抑制白花丹素介导的ROS产生和凋亡。白花丹素处理还导致负责ROS代谢的基因表达改变，包括超氧化物歧化酶2（Mn-SOD）。
本研究表明ROS在白花丹素诱导的人前列腺癌细胞凋亡中起重要作用。
