Abstract
The increased expression of cyclooxygenase (COX)-2 significantly enhances carcinogenesis and inflammatory reactions, and its regulation may be a reasonable target for cancer chemoprevention. We demonstrated previously that deguelin inhibits proliferation of premalignant human bronchial epithelial (HBE) cells, such as 1799 cells and squamous HBE cells, by regulating phosphatidylinositol-3-kinase Akt activity, which is involved in COX-2 expression. We sought to determine the effect of deguelin on COX-2 expression in squamous HBE cells. Deguelin strongly inhibited COX-2 expression in squamous HBE cells, without affecting the COX-1 protein level. Deguelin inhibited proliferation of a variety of non-small cell lung carcinoma (NSCLC) cell lines through apoptosis and induced Bax expression in the H322 NSCLC and squamous HBE cells. Deguelin treatment did not affect Bcl-2 protein levels but increased expression levels of the proapoptotic protein p53 and the cyclin-dependent kinase inhibitors p21 and p27 in the squamous HBE cells. The sensitivity of the squamous HBE and NSCLC cells to deguelin and the inhibitory effects of deguelin on COX-2 expression in the squamous HBE cells indicate that regulation of COX-2 expression is involved in the chemopreventive action of deguelin in lung cancer.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Apoptosis
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Blotting, Western
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Bronchi / metabolism*
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Carcinoma, Non-Small-Cell Lung / metabolism*
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Carcinoma, Non-Small-Cell Lung / prevention & control
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Cell Cycle Proteins / metabolism
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Cell Division
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Cell Line, Tumor
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Cells, Cultured
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclins / metabolism
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Cyclooxygenase 2
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Dose-Response Relationship, Drug
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Epithelial Cells / metabolism*
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Humans
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Immunoblotting
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Isoenzymes / antagonists & inhibitors*
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Isoenzymes / biosynthesis*
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Lung Neoplasms / metabolism*
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Lung Neoplasms / prevention & control
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Male
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Membrane Proteins
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Phosphatidylinositol 3-Kinases / metabolism
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Prostaglandin-Endoperoxide Synthases / biosynthesis*
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Rotenone / analogs & derivatives*
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Rotenone / pharmacology*
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Time Factors
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Tumor Suppressor Protein p53 / metabolism
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Tumor Suppressor Proteins / metabolism
Substances
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CDKN1A protein, human
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Isoenzymes
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Membrane Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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Rotenone
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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deguelin