title: Inhibition of hypoxia-induced epithelial mesenchymal transition by luteolin             in non-small cell lung cancer cells.
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.
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, PR China.
authors.forename: Junshan
authors.initials: J
authors.lastname: Ruan
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Linggeng
authors.initials: L
authors.lastname: Yan
authors.forename: Yuping
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yue
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Ai-Yun
authors.initials: AY
authors.lastname: Wang
authors.forename: Wenxing
authors.initials: W
authors.lastname: Chen
authors.forename: Shizhong
authors.initials: S
authors.lastname: Zheng
authors.forename: Shaoming
authors.initials: S
authors.lastname: Wang
authors.forename: Yin
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D047311:Luteolin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D039641:Integrin beta Chains; D051416:Focal Adhesion Protein-Tyrosine Kinases; D047311:Luteolin