Inhibitory effects of dieckol on hypoxia-induced epithelial-mesenchymal transition of HT29 human colorectal cancer cells.

Abstract

Hypoxia-induced epithelial-mesenchymal transition (EMT) has been identified as essential for tumor progression and metastasis. The present study examined the effects of an antioxidant, dieckol, on hypoxia-induced EMT in HT29 human colorectal cancer cells. HT29 cells were treated with a hypoxia-inducing agent, CoCl2, and an increase in the levels of intracellular reactive oxygen species (ROS) and various morphological changes, such as loss of cell-cell contact and aggressive cell migration were observed. CoCl2 also induced an increase in the expression of hypoxia-inducible factor 1α (HIF1α) and various mesenchymal-specific markers, including vimentin and snail family transcriptional repressor 1 (Snail1), and a decrease in the expression of E-cadherin, thus suggesting that CoCl2 induced EMT in HT29 cells. Conversely, the CoCl2-induced EMT of HT29 cells was suppressed following treatment with dieckol. In addition, ROS generation, EMT marker protein expression and intracellular localization, cell migration and cell invasion were attenuated following dieckol treatment. The findings of the present study suggested that dieckol may inhibit hypoxia-induced EMT in HT29 cells by regulating the levels of cellular ROS and protein expression levels downstream of the HIF1α signaling pathway. Therefore, dieckol has the potential to become an attractive therapeutic agent for the treatment of colorectal cancer.