Evaluation of cytotoxicity of propofol and its related mechanism in glioblastoma cells and astrocytes

• Published in: Environmental toxicology Vol. 32; no. 12; pp. 2440 - 2454
• Main Authors: Hsu, Shu‐Shong, Jan, Chung‐Ren, Liang, Wei‐Zhe
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-12-2017
• Subjects: Acetylcysteine; Acetylcysteine - pharmacology; Amino Acid Chloromethyl Ketones - pharmacology; Animal models; Animals; Anticancer properties; Antineoplastic Agents - pharmacology; Antioxidants; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Astrocytes; Astrocytes - cytology; Astrocytes - drug effects; BAX protein; Bcl-2 protein; Brain cancer; Caspase; Caspase 3 - metabolism; Caspase 9 - metabolism; Caspase Inhibitors - pharmacology; Caspase-3; Caspase-9; Catalase; Cell cycle; Cell Cycle - drug effects; cell cycle arrest; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cyclin B1; Cytotoxicity; Evaluation; Glioblastoma; Glioblastoma cells; Glutathione; Glutathione peroxidase; GTP-binding protein; Humans; Hydrogen peroxide; Oxidative stress; p53 Protein; Pain; Peroxidase; propofol; Propofol - pharmacology; Proteins; Rats; Reactive Oxygen Species - metabolism; ROS; Stress concentration; Superoxide dismutase; Toxicity; apoptosis; astrocytes; cell cycle arrest; propofol; glioblastoma cells; ROS
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.22458

Propofol (2,6‐diisopropylphenol), one of the extensively and commonly used anesthetic agents, has been shown to affect the biological behavior of various models. Previous researches have shown that propofol‐induced cytotoxicity might cause anticancer effect in different cells. However, the mechanisms underlying the effect of propofol on cytotoxicity is still elusive in human glioblastoma cells. The aims of this study were to evaluate effects of propofol on cytotoxicity, cell cycle distribution and ROS production, and establish the relationship between oxidative stress and cytotoxicity in GBM 8401 human glioblastoma cells and DI TNC1 rat astrocytes. Propofol (20–30 μM) concentration‐dependently induced cytotoxicity, cell cycle arrest, and increased ROS production in GBM 8401 cells but not in DI TNC1 cells. In GBM 8401 cells, propofol induced G2/M phase cell arrest, which affected the CDK1, cyclin B1, p53, and p21 protein expression levels. Furthermore, propofol induced oxygen stresses by increasing
O2− and H2O2 levels but treatment with the antioxidant N‐acetylcysteine (NAC) partially reversed propofol‐regulated antioxidative enzyme levels (superoxide dismutase, catalase, and glutathione peroxidase). Most significantly, propofol induced apoptotic effects by decreasing Bcl‐2 but increasing Bax, cleaved caspase‐9/caspase‐3 levels, which were partially reversed by NAC. Moreover, the pancaspase inhibitor Z‐VAD‐FMK also partially prevented propofol‐induced apoptosis. Together, in GBM 8401 cells but not in DI TNC1 cells, propofol activated ROS‐associated apoptosis that involved cell cycle arrest and caspase activation. These findings indicate that propofol not only can be an anesthetic agent which reduces pain but also has the potential to be used for the treatment of human glioblastoma.