Inhibition of hypoxia-induced epithelial mesenchymal transition by luteolin in non-small cell lung cancer cells.

Hypoxia-induced epithelial mesenchymal transition (EMT) is an essential step in cancer metastasis. Luteolin, a flavonoid that is widely distributed in plants, is a novel anticancer agent. However, the mechanism underlying its anticancer effects remains undefined. In this study, for the first time, we demonstrate that luteolin inhibits hypoxia-induced EMT in human non-small cell lung cancer cells in culture, which is demonstrated by the fact that hypoxia-induced EMT reduced the expression of E-cadherin and other epithelial markers and increased the expression of N-cadherin, vimentin and other mesenchymal markers; these effects were markedly attenuated by luteolin. In addition, luteolin also inhibited hypoxia-induced proliferation, motility and adhesion in the cells. Furthermore, we reveal that luteolin inhibits the expression of integrin β1 and focal adhesion kinase (FAK).Since integrin β1 and FAK signaling are closely related to EMT formation, these results suggest that luteolin inhibits hypoxia-induced EMT, at least in part, by inhibiting the expression of integrin β1 and FAK.