Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Thymol inhibits cell migration and invasion by downregulating the activation of PI3K/AKT and ERK pathways in human colon cancer cells

Ran Lv¹, Zhenzhou Chen²

¹Gastroenterology Department of Chinese Medicine, China-Japan Friendship Hospital, Beijing 100029; ²General Surgery Department, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China.

For correspondence:- Zhenzhou Chen Email: chenzhenzhou6@gmail.com Tel:+861084013135

Accepted: 24 November 2017 Published: 29 December 2017

Citation: Lv R, Chen Z. Thymol inhibits cell migration and invasion by downregulating the activation of PI3K/AKT and ERK pathways in human colon cancer cells. Trop J Pharm Res 2017; 16(12):2895-2901 doi: 10.4314/tjpr.v16i12.13

© 2017 The authors.
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Abstract

Purpose: To assess the anti-metastasis effects of thymol on human colorectal cancer cells.

Methods: Human colorectal adenocarcinoma cell HT29 was incubated with varying concentrations of thymol. Cell viability, migration and invasion were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dipheny-tetrazoliumbromide (MTT) and Transwell assays, respectively. Matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) were analyzed by gel zymogram assay. Epithelial-mesenchymal transition (EMT)-associated gene expression and signaling pathway were analyzed using real-time quantitative polymerase chain reaction (PCR) and Western blotting, respectively.

Results: Thymol was significantly inhibited migration and invasion of HT29 cell (p < 0.01) and also markedly reduced the activity of matrix degrading enzymes MMP-2 and MMP-9 (p < 0.01). Moreover, the epithelial marker, E-cadherin, was elevated, while mesenchymal markers (vimentin and α-SMA), and associated transcription factors (snail and slug) decreased after thymol treatment (p < 0.01). In addition, thymol inhibited the phosphorylation of PI3K/AKT and ERK pathways (p < 0.01).

Conclusion: Thymol efficiently attenuates cell migration and invasion by decreasing EMT and downregulating the activation of PI3K/AKT and ERK signaling pathways in colorectal adenocarcinoma cells. It is, thus, a potential candidate drug for the management of colorectal cancer

Keywords: Thymol, Colorectal cancer, Anti-metastasis, Epithelial-mesenchymal transition, Vimentin, PI3K/AKT and ERK pathway