Cheng Yanhao, Dai Chao, Zhang Jian
Department of Functional Neurosurgery, The People's Hospital of Linyi, Linyi 276003, Shandong, China.
Acta Biochim Pol. 2017;64(2):343-350. doi: 10.18388/abp.2016_1438. Epub 2017 Jun 2.
Glioma is the most prevalent type of adult primary brain tumor and chemotherapy of glioma was limited by drug-resistance. Linalool is an acyclic monoterpene alcohol possessing various pharmacological activities. The present study was conducted to evaluate the effect of linalool on glioma cell growth. The effect of linalool on cell viability in U87-MG cells was investigated and the results showed that linalool significantly reduced cell viability in a concentration- and time-dependent manner. In addition, exposure of the cells to linalool resulted in a concentration-dependent increase of TUNEL-stained cells, indicating the occurrence of apoptotic cell death. Linalool decreased mitochondrial oxygen consumption rate, increased the expression of Bax and Bak, reduced the expression of Bcl-2 and Bcl-xl, and increased the activities of caspase 3 and caspase 9, leading to increase of apoptosis. Linalool resulted in a concentration-dependent decrease of SOD activity but had no significant effect on mRNA and protein expression of SOD2. Moreover, linalool resulted in a significant increase of the expression of acetylated SOD2. The mRNA and protein expression of SIRT3 was significantly inhibited by linalool. Immunoblot analysis showed that there was an evident protein/protein interaction between SOD2 and SIRT3 under normal condition. Linalool treatment significantly decreased the interaction between SOD2 and SIRT3. Overexpression of SIRT3 significantly inhibited linalool-induced increase of mitochondrial ROS production and apoptotic cell death, and decrease of cell viability. In summary, the data demonstrated that linalool exhibited inhibitory effect on glioma cells through regulation of SIRT3-SOD2-ROS signaling.
胶质瘤是成人原发性脑肿瘤中最常见的类型，胶质瘤的化疗受到耐药性的限制。芳樟醇是一种具有多种药理活性的无环单萜醇。本研究旨在评估芳樟醇对胶质瘤细胞生长的影响。研究了芳樟醇对U87-MG细胞活力的影响，结果表明芳樟醇以浓度和时间依赖性方式显著降低细胞活力。此外，将细胞暴露于芳樟醇会导致TUNEL染色细胞呈浓度依赖性增加，表明发生了凋亡性细胞死亡。芳樟醇降低线粒体氧消耗率，增加Bax和Bak的表达，降低Bcl-2和Bcl-xl的表达，并增加caspase 3和caspase 9的活性，从而导致凋亡增加。芳樟醇导致SOD活性呈浓度依赖性降低，但对SOD2的mRNA和蛋白表达无显著影响。此外，芳樟醇导致乙酰化SOD2的表达显著增加。芳樟醇显著抑制SIRT3的mRNA和蛋白表达。免疫印迹分析表明，在正常条件下SOD2和SIRT3之间存在明显的蛋白/蛋白相互作用。芳樟醇处理显著降低了SOD2和SIRT3之间的相互作用。SIRT3的过表达显著抑制了芳樟醇诱导的线粒体ROS产生增加、凋亡性细胞死亡以及细胞活力降低。总之，数据表明芳樟醇通过调节SIRT3-SOD2-ROS信号通路对胶质瘤细胞表现出抑制作用。
