SIRT3-SOD2-ROS pathway is involved in Linalool-induced glioma cell apoptotic death

Yanhao Cheng; Chao Dai; Jian Zhang

doi:10.18388/abp.2016_1438

Yanhao Cheng
Chao Dai The People’s Hospital of Linyi
Jian Zhang

DOI: https://doi.org/10.18388/abp.2016_1438

Keywords: Linalool, Glioma, Apoptotic cell death, SIRT3, SOD2

Abstract

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 U87-MG cells was investigated and the results showed that Linalool significantly reduced cell viability in U87-MG cells in a concentration and time-dependent manner. In addition, exposure of cells to Linalool resulted in 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 Bcl-2, 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 the mRNA and protein expression of SOD2. Moreover, Linalool resulted in a significant increase of acetylated SOD2. The mRNA and protein expression of SIRT3 was significantly inhibited by Linalool. Immunoblot analysis showed that there were protein/protein interaction of SOD2 and SIRT3 in control U87-MG cells. Linalool treatment significantly decreased the interaction of SOD2 and SIRT3. Overexpression of SIRT3 significantly inhibited Linalool-induced increase of mitochondrial ROS level, apoptotic cell death and decrease of cell viability. In summary, we found that Linalool exhibited inhibitory effect on glioma cells through regulation of SIRT3-SOD2-ROS signaling.

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