Thymol Isolated from Thymus vulgaris L. Inhibits Colorectal Cancer Cell Growth and Metastasis by Suppressing the Wnt/β-Catenin Pathway

Drug Des Devel Ther. 2020 Jul 1:14:2535-2547. doi: 10.2147/DDDT.S254218. eCollection 2020.

Abstract

Purpose: Colorectal cancer (CRC) is one of the most commonly occurring cancers and is associated with high morbidity and mortality. Nevertheless, there is currently no safe and effective treatment for this condition. Thymol is a phenolic compound that is recognized as safe for use in food as well as medical and cosmetic fields. Increasing evidence has indicated that thymol exerts prominent antitumor effects in a variety of cancers, including CRC. However, how thymol elicits these effects on CRC and the associated underlying mechanisms remains unclear.

Methods: HCT116 and Lovo cells were treated with different concentrations of thymol. Cell Counting Kit-8 (CCK-8) and transwell migration and invasion assays were used to evaluate cell proliferation, migration, and invasion, respectively. Cell apoptosis and cell cycle distribution were measured by flow cytometry. RT-qPCR, Western blot, and immunohistochemistry were used to detect the expression of related genes and their protein products.

Results: In this study, we tested the antitumor activity of thymol extracted from a Chinese medicinal herb, Thymus vulgaris L. We show that thymol treatment in vitro inhibited cell proliferation and induced apoptosis and cell cycle arrest in CRC. Furthermore, in vivo treatment with 75 and 150 mg/kg thymol led to a significant decrease in tumor volume. Thymol administration induced CRC cell apoptosis through activation of the BAX/Bcl-2 signaling pathway. In addition, thymol suppressed CRC cell epithelial-mesenchymal transition (EMT), invasion, and metastasis via inhibiting the activation of the Wnt/β-catenin pathway, both in vitro and in vivo.

Conclusion: Thymol may prevent CRC progression through inhibition of the Wnt/β-catenin signaling pathway, highlighting its potential as a novel therapeutic option for the treatment of CRC.

Keywords: Wnt/β-catenin; colorectal cancer; thymol; tumor growth and metastasis.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Drug Screening Assays, Antitumor
  • Humans
  • Thymol / chemistry
  • Thymol / isolation & purification
  • Thymol / pharmacology*
  • Thymus Plant / chemistry*
  • Wnt Signaling Pathway / drug effects
  • beta Catenin / antagonists & inhibitors*
  • beta Catenin / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • beta Catenin
  • Thymol

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (81860509) and Joint Foundation of Kunming Medical University and Yunnan Provincial Science and Technology Department (2017FE467-159), and grants from the Internal Division of Yunnan Provincial Health Commission (2016NS226, 2017NS249) and Yunnan provincial foundation for medical academic leader (D-2017002, 2018HB049).