Thymol Enhances 5-Fluorouracil Cytotoxicity by Reducing Migration and Increasing Apoptosis and Cell Cycle Arrest in...

Esophageal cancer (EC) is a common cancer globally and has a low survival rate because it is often diagnosed at a late-stage, and is frequently chemotherapy resistant. Thymol is found in the herb thyme and has been reported to have potential anticancer properties. We aimed to explore the effects of thymol on the efficacy of 5-Fluorouracil (5-FU) treatment in an in vitro model of EC. We evaluated the synergistic effects of thymol with 5-FU using cell viability, apoptosis, cell cycle analysis, scratch wound healing assay, gelatin zymography, as well as reactive oxygen species (ROS) generation aproaches. The results indicated that thymol significantly decreased the viability of KYSE-30 cells in a time and dose-dependently. However, thymol had a minimal cytotoxic effect against normal fibroblasts. In addition, thymol significantly increased the chemosensitivity of EC KYSE-30 cells to 5-FU by promoting early and late apoptosis, inducing Sub-G1 and G2/M cell cycle arrest, and increasing ROS generation. Combination therapy of thymol with 5-FU also resulted in an increased expression of p53 and Bax, decreased expression of Bcl2, reduced activity of MMP-2, and reduced cell migration compared to single therapies. These findings suggest that thymol has the potential to promote the anticancer potency of 5-FU chemotherapy and inhibit metastasis. However, further studies using animal models are necessary to validate these results.