title: Green tea inhibits cycolooxygenase-2 in non-small cell lung cancer cells through the induction of Annexin-1.
abstract: Elevated cyclooygenase-2 (COX-2) expression is frequently observed in human non-small cell lung cancer (NSCLC) and associated with poor prognosis, indicating critical involvement of the inflammatory pathway in lung carcinogenesis. Recently, we found that green tea extract (GTE) induced Annexin-1 (ANX1) in the lung adenocarcinoma A549 cells. ANX1 is a glucocorticoid-inducible 37kDa protein involved in a wide range biological function and is an important anti-inflammatory mediator. The present study further examines the interplay between the expressions and production of ANX1, COX-2, phospholipase A(2) (cPLA(2)) and prostaglandin E(2) (PGE(2)) following the treatment of NSCLC cell lines with GTE. We found that GTE induced ANX1 and inhibited COX-2 expression in lung cancer A549, H157 and H460 cell lines. Addition of pro-inflammatory cytokine IL-1β diminished GTE-induced ANX1. Silence of ANX1 in cells abrogates the inhibitory activity on COX-2, indicating that the anti-inflammatory activity of GTE is mediated at least partially by the up-regulation of ANX1. However, differential pattern of inhibitory effects of ANX1 on cPLA(2) expression was observed among various cell types, suggesting that the anti-inflammatory activity mediated by ANX1 is cell type specific. Our study may provide a new mechanism of GTE on the prevention of lung cancer and other diseases related to inflammation.
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. qlu@mednet.ucla.edu
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Lu
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Jin
authors.forename: Jenny T
authors.initials: JT
authors.lastname: Mao
authors.forename: Zuo-Feng
authors.initials: ZF
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Heber
authors.forename: Steven M
authors.initials: SM
authors.lastname: Dubinett
authors.forename: Jianyu
authors.initials: J
authors.lastname: Rao
mesh_terms: D017305:Annexin A1 / Q000096:biosynthesis*; D028241:Camellia sinensis / Q000737:chemistry*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000201:enzymology*; D054510:Phospholipases A2, Cytosolic / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D017305:Annexin A1; D052246:Cyclooxygenase 2 Inhibitors; D010936:Plant Extracts; D051546:Cyclooxygenase 2; D054510:Phospholipases A2, Cytosolic; D015232:Dinoprostone