Inhibitory effect of dieckol on hypoxia-induced epithelial-to-mesenchymal transition of HT29 human colorectal cancer cells

Abstract

Hypoxia-induced epithelial-mesenchymal transition (EMT) is essential for tumor progression and metastasis. Here, we examined the effect of anti-oxidant, dieckol, on hypoxia-induced EMT of HT29 human colorectal cancer cells. HT29 cells treated with the hypoxia-inducing agent, CoCl2, exhibited an increase in levels of intracellular reactive oxygen species (ROS) as well as certain morphological changes, including loss of cell-cell contact and aggressive cell migration and invasion. CoCl2 also induced an increase in hypoxia-induced factor 1α (HIF 1α) expression and the mesenchymal-specific marker, Vimentin, a decrease in expression of the epithelial specific marker E-cadherin, suggesting that the CoCl2-induced changes characteristic to HT29 cells represent EMT. The CoCl2-induced EMT of HT29 cells was suppressed by dieckol treatment. Furthermore, ROS generation, EMT marker protein expression, distribution, cell migration, and Matrigel invasion were conversely regulated. Taken together, our findings suggest that dieckol inhibits hypoxia-induced EMT of HT29 cells by regulating the levels of cellular ROS and gene expression downstream of the HIF 1α signaling pathway. Dieckol has the potential to become an attractive therapeutic agent for colorectal cancer cells.