Farid Qoorchi Moheb Seraj1, Niloofar Heravi-Faz2, Arash Soltani3, Seyed Sajad Ahmadi4, Fatemeh Shahbeiki5, Amir Talebpour6, Amir R Afshari7, Gordon A Ferns8, Afsane Bahrami9,10. 1. Endovascular Section, Neurosurgical Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Department of Molecular Genetics, Faculty of Sciences, Neyshabour branch, Islamic Azad University, Neyshabour, Iran. 3. Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 4. Department of Ophthalmology, Khatam Ol-Anbia Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. 5. Department of Medical Laboratory Sciences, Mashhad branch, Islamic Azad University, Mashhad, Iran. 6. Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran. 7. Department of Physiology and Pharmacology, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran. 8. Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, BN1 9PH, Sussex, UK. 9. Clinical Research Development Unit, Faculty of Medicine, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. BahramiAF@mums.ac.ir. 10. Clinical Research Development Unit of Akbar Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. BahramiAF@mums.ac.ir.
Abstract
BACKGROUND: Thymol (2-isopropyl-5-methylphenol) is a colorless crystalline derivative of cymene, that possesses pleotropic pharmacological properties, including analgesic, antibacterial, antispasmodic, and anti-inflammatory activities. Thymol has also been recognized for its beneficial effect as an anti-tumor agent, but the precise mechanism for this has not been fully elucidated. We aimed to identifying whether thymol exerts anti-cancer activity in human U-87 malignant glioblastoma (GB) cells (U-87). METHODS AND RESULTS: Cell viability and apoptosis was evaluated in U-87 cells treated with thymol at different concentrations. Reactive oxygen species (ROS) production, mRNA expressions of apoptosis-related genes and cell cycle characteristics were assessed. The cytotoxic activity of the co-exposure of thymol and temozolomide (TMZ) was also evaluated. The half-maximal inhibitory concentration (IC50) of thymol in the U-87 cells was 230 μM assessed at 24 h after exposure. Thymol did not exhibit any cytotoxic effects on normal L929 cells at this concentration. Thymol treatment increased the expression of Bax and p53, and also increased apoptotic cell death, and excessive generation of ROS. Moreover, the cytotoxic activity of thymol on the U-87 cells may be related to the arrest of the cell cycle at the G0/G1 interface. Combination therapy showed that the cytotoxic effects of thymol synergized with TMZ, and combined treatment had more cytotoxic potential compared to either of the agents alone. CONCLUSIONS: Our data indicate the potential cytotoxic activities of thymol on U-87 cells. Further studies are required to evaluate the spectrum of the antitumor activity of thymol on GB cells.
BACKGROUND: Thymol (2-isopropyl-5-methylphenol) is a colorless crystalline derivative of cymene, that possesses pleotropic pharmacological properties, including analgesic, antibacterial, antispasmodic, and anti-inflammatory activities. Thymol has also been recognized for its beneficial effect as an anti-tumor agent, but the precise mechanism for this has not been fully elucidated. We aimed to identifying whether thymol exerts anti-cancer activity in human U-87 malignant glioblastoma (GB) cells (U-87). METHODS AND RESULTS: Cell viability and apoptosis was evaluated in U-87 cells treated with thymol at different concentrations. Reactive oxygen species (ROS) production, mRNA expressions of apoptosis-related genes and cell cycle characteristics were assessed. The cytotoxic activity of the co-exposure of thymol and temozolomide (TMZ) was also evaluated. The half-maximal inhibitory concentration (IC50) of thymol in the U-87 cells was 230 μM assessed at 24 h after exposure. Thymol did not exhibit any cytotoxic effects on normal L929 cells at this concentration. Thymol treatment increased the expression of Bax and p53, and also increased apoptotic cell death, and excessive generation of ROS. Moreover, the cytotoxic activity of thymol on the U-87 cells may be related to the arrest of the cell cycle at the G0/G1 interface. Combination therapy showed that the cytotoxic effects of thymol synergized with TMZ, and combined treatment had more cytotoxic potential compared to either of the agents alone. CONCLUSIONS: Our data indicate the potential cytotoxic activities of thymol on U-87 cells. Further studies are required to evaluate the spectrum of the antitumor activity of thymol on GB cells.
Authors: Abolfazl Maghrouni; Maryam Givari; Mohammad Jalili-Nik; Hamid Mollazadeh; Bahram Bibak; Mohammad Montazami Sadeghi; Amir R Afshari; Thomas P Johnston; Amirhossein Sahebkar Journal: Int Immunopharmacol Date: 2021-02-12 Impact factor: 4.932