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Published on: February 27, 2016
SIRT3-SOD2-ROS pathway is involved in linalool-induced glioma cell apoptotic death
Yanhao Cheng1, Chao Dai1, Jian Zhang1
1Department of Functional Neurosurgery, The People's Hospital of Linyi, Linyi 276003, Shandong, China.
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 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.
Insights
Linalool, a natural compound, effectively inhibits glioma cell growth by inducing apoptosis. It achieves this by regulating the SIRT3-SOD2-ROS signaling pathway, offering a potential new avenue for brain tumor treatment.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Pharmacology
Background:
- Glioma is the most common primary brain tumor in adults.
- Chemotherapy for glioma faces challenges due to drug resistance.
- Linalool is a monoterpene alcohol with diverse pharmacological properties.
Purpose of the Study:
- To investigate the anti-glioma effects of linalool.
- To elucidate the molecular mechanisms underlying linalool's action on glioma cells.
Main Methods:
- Cell viability assays (MTT) were performed on U87-MG glioma cells.
- Apoptosis was assessed using TUNEL staining and Western blot analysis of apoptosis-related proteins (Bax, Bak, Bcl-2, Bcl-xl, Caspase 3, Caspase 9).
- Mitochondrial function, SOD activity, SIRT3 and SOD2 expression, acetylation, and protein interactions were analyzed.
Main Results:
- Linalool significantly reduced glioma cell viability and induced apoptosis in a dose- and time-dependent manner.
- Linalool altered mitochondrial function, increased pro-apoptotic markers, and decreased anti-apoptotic markers.
- Linalool modulated the SIRT3-SOD2-ROS pathway, decreasing SIRT3 expression and SOD2-SIRT3 interaction, which was linked to increased ROS and apoptosis.
Conclusions:
- Linalool exhibits significant anti-glioma activity by promoting apoptosis.
- The mechanism involves the regulation of the SIRT3-SOD2-ROS signaling pathway.
- Linalool represents a potential therapeutic agent for glioma treatment.
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