Thymol inhibits cell migration and invasion by downregulating the activation of PI3K/AKT and ERK pathways in human colon cancer cells
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, 5dipheny-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