Thymol has anticancer effects in U-87 human malignant glioblastoma cells

Mol Biol Rep. 2022 Oct;49(10):9623-9632. doi: 10.1007/s11033-022-07867-3. Epub 2022 Aug 23.

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.

Keywords: Apoptosis; Cell cycle arrest; Glioma; ROS; Thymol.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Antineoplastic Agents* / pharmacology
  • Apoptosis
  • Cell Line, Tumor
  • Cymenes
  • Glioblastoma* / drug therapy
  • Glioblastoma* / pathology
  • Humans
  • Parasympatholytics / pharmacology
  • Parasympatholytics / therapeutic use
  • RNA, Messenger
  • Reactive Oxygen Species / metabolism
  • Temozolomide / pharmacology
  • Thymol / pharmacology
  • Thymol / therapeutic use
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Cymenes
  • Parasympatholytics
  • RNA, Messenger
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Thymol
  • Temozolomide