Fu Yujie, Kadioglu Onat, Wiench Benjamin, Wei Zuofu, Gao Chang, Luo Meng, Gu Chengbo, Zu Yuangang, Efferth Thomas
Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China; Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin, China.
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
Phytomedicine. 2015 Apr 15;22(4):462-8. doi: 10.1016/j.phymed.2015.02.005. Epub 2015 Mar 11.
The low abundant cajanin stilbene acid (CSA) from Pigeon Pea (Cajanus cajan) has been shown to kill estrogen receptor α positive cancer cells in vitro and in vivo. Downstream effects such as cell cycle and apoptosis-related mechanisms have not been analyzed yet.
We analyzed the activity of CSA by means of flow cytometry (cell cycle distribution, mitochondrial membrane potential, MMP), confocal laser scanning microscopy (MMP), DNA fragmentation assay (apoptosis), Western blotting (Bax and Bcl-2 expression, caspase-3 activation) as well as mRNA microarray hybridization and Ingenuity pathway analysis.
CSA induced G2/M arrest and apoptosis in a concentration-dependent manner from 8.88 to 14.79 µM. The MMP broke down, Bax was upregulated, Bcl-2 downregulated and caspase-3 activated. Microarray profiling revealed that CSA affected BRCA-related DNA damage response and cell cycle-regulated chromosomal replication pathways.
CSA inhibited breast cancer cells by DNA damage and cell cycle-related signaling pathways leading to cell cycle arrest and apoptosis.
木豆中含量较低的木豆芪酸（CSA）已被证明在体外和体内均可杀死雌激素受体α阳性癌细胞。然而，尚未分析其下游效应，如细胞周期和凋亡相关机制。
我们通过流式细胞术（细胞周期分布、线粒体膜电位、MMP）、共聚焦激光扫描显微镜（MMP）、DNA片段化分析（凋亡）、蛋白质印迹法（Bax和Bcl-2表达、caspase-3激活）以及mRNA微阵列杂交和 Ingenuity 通路分析来分析CSA的活性。
CSA在8.88至14.79µM浓度范围内以浓度依赖的方式诱导G2/M期阻滞和凋亡。MMP被破坏，Bax上调，Bcl-2下调，caspase-3激活。微阵列分析表明，CSA影响与BRCA相关的DNA损伤反应和细胞周期调节的染色体复制途径。
CSA通过DNA损伤和细胞周期相关信号通路抑制乳腺癌细胞，导致细胞周期阻滞和凋亡。
