Thymol Elicits HCT-116 Colorectal Carcinoma Cell Death Through Induction of Oxidative Stress

Anticancer Agents Med Chem. 2018 Feb 7;17(14):1942-1950. doi: 10.2174/1871520617666170327121228.

Abstract

Background: Colon cancer is one of the most deadly and common carcinomas occurring worldwide and there have been many attempts to treat this cancer. The present work was designed in order to evaluate thymol as a potent drug against colon cancer.

Materials and methods: Cytotoxicity of thymol at different concentrations was evaluated against a human colon carcinoma cell line (HCT-116 cells). Fluorescent staining was carried out to evaluate the level of ROS as well as mitochondrial and DNA fragmentation and immunoblot analysis were performed to confirm apoptosis and mitoptosis.

Results and conclusion: Results of the study demonstrated that thymol efficiently created an oxidative stress environment inside HCT-116 cells, a colorectal carcinoma cell line, through induction of ROS production along with intense damage to DNA and mitochondria, as observed through Hoechst and rhodamine 123 staining, respectively. Moreover, expression of PARP-1, p-JNK, cytochrome-C and caspase-3 proteins was up-regulated, suggesting HCT-116 cells underwent mitoptotic cell death. Therefore, thymol could be used as a potent drug against colon cancer due to its lower toxicity and prevalence in natural medicinal plants.

Keywords: Thymol; cell death.; colon carcinoma; mitochondrial fragmentation; mitoptosis; oxidative stress.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Death / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colorimetry
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HCT116 Cells
  • Humans
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Structure-Activity Relationship
  • Thymol / chemistry
  • Thymol / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Thymol