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

Abstract

Abstract. 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.

HIF‐1α/VEGF signaling‐mediated epithelial–mesenchymal transition and angiogenesis is critically involved in anti‐metastasis effect of luteolin in melanoma cells

“…*p < 0.05 and **p < 0.01 indicate a significant difference from the control group compounds targeting EMT and angiogenesis have been the efficient therapeutic approach for the treatment of metastatic cancers . Luteolin, a flavonoid that is found in more than 300 plant species, has recently been shown to inhibit a variety of cancers, both in vitro and in vivo, with little to minimal toxicity (Lu et al, 2015;Ruan et al, 2012). Previous studies have shown that luteolin inhibits metastasis of triple-negative breast cancer cells through suppressing EMT (Cook et al, 2017).…”

Natural Polyphenols for Prevention and Treatment of Cancer

“…Luteolin treatment (5–50 μM) to non-small lung cancer cells could inhibit hypoxia-induced EMT as well as cell viability, proliferation and motility. The effect was at least partly through suppressing the expression of integrin β1 and FAK [87]. More importantly, luteolin administration (i.p.…”

Molecular targets of luteolin in cancer

“…Luteolin inhibits the expression of integrin β1 and focal adhesion kinase (FAK), which are closely related to EMT formation. This relationship suggests that luteolin inhibits hypoxia-induced EMT, at least in part, by inhibiting the expression of integrin β1 and FAK ( Ruan et al , 2012a ). Luteolin also inhibits EMT in malignant melanoma cells both in vitro and in vivo by regulating β3 integrin ( Ruan et al , 2012b ).…”