Melatonin inhibits epithelial-to-mesenchymal transition in gastric cancer cells via attenuation of IL-1 /NF-?B/MMP2/MMP9 signaling

Abstract

Although melatonin has been shown to exert marked antitumor effects against a variety of cancers, the underlying mechanisms remain to be fully elucidated. It has been hypothesized that the anticancer properties of melatonin are associated with its ability to suppress epithelial-to-mesenchymal transition (EMT) of cancer cells. In the present study, melatonin effectively suppressed interleukin (IL)-1 -induced EMT in human gastric adenocarcinoma (GA) cells. Sequential treatment of GA cells with melatonin after IL-1 challenge markedly reversed the IL-1 -induced morphological changes, reduced cell invasion and migration, increased -catenin and E-cadherin expression, and downregulated fibronectin, vimentin, Snail, matrix metalloproteinase (MMP)2 and MMP9 expression. Moreover, IL-1 -induced activation of NF-?B was attenuated following treatment with melatonin. Knockdown of NF-?B significantly reduced the IL-1 -induced EMT in GA cells. Taken together, these findings indicate that melatonin may act by suppressing EMT and tumor progression by inhibiting NF-?B activity.