Gamma-aminobutyric acid, a potential tumor suppressor for small airway-derived lung adenocarcinoma.

Abstract:

:Pulmonary adenocarcinoma (PAC) is the leading type of lung cancer in smokers and non-smokers that arises in most cases from small airway epithelial cells. PAC has a high mortality due to its aggressive behavior and resistance to cancer therapeutics. We have shown previously that the proliferation of human PAC cells NCI-H322 and immortalized human small airway epithelial cells HPL1D is stimulated by cyclic adenosine monophosphate (cAMP)/protein kinase A-dependent phosphorylation of cyclic adenosine monophosphate response element-binding (CREB) protein and transactivation of the epidermal growth factor receptor and that this pathway is activated by beta-1-adrenoreceptors (beta(1)-ARs) and the non-genomic estrogen receptor beta. Our current in vitro studies with HPL1D and NCI-H322 cells showed that signaling via the gamma-amino butyric acid receptor (GABA(B)R) strongly inhibited base level and isoproterenol-induced cAMP, p-CREB, cyclic adenosine monophosphate response element-luciferase activity and p-extracellular regulated kinase-1 (ERK1)/2 and effectively blocked DNA synthesis and cell migration. The inhibitory effects of gamma-amino butyric acid (GABA) were disinhibited by the GABA(B)R antagonist CGP-35348 or GABA(B)R knockdown. Immunohistochemical investigation of hamster lungs showed significant underexpression of GABA in animals with small airway-derived PACs induced by the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These findings suggest that GABA may have tumor suppressor function in small airway epithelia and the PACs derived from them and that downregulation of GABA by NNK may contribute to the development of this cancer in smokers. Our findings suggest that marker-guided treatment with GABA or a GABA(B)R agonist of individuals with downregulated pulmonary GABA may provide a novel targeted approach for the prevention of PAC in smokers.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Schuller HM,Al-Wadei HA,Majidi M

doi

10.1093/carcin/bgn041

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

1979-85

issue

10

eissn

0143-3334

issn

1460-2180

pii

bgn041

journal_volume

29

pub_type

杂志文章
  • Enhanced glycolysis, regulated by HIF-1α via MCT-4, promotes inflammation in arsenite-induced carcinogenesis.

    abstract::Arsenite is well established as a human carcinogen, but the molecular mechanisms leading to arsenite-induced carcinogenesis are complex and elusive. Accelerated glycolysis, a common process in tumor cells called the Warburg effect, is associated with various biological phenomena. However, the role of glycolysis induce...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgx034

    authors: Luo F,Zou Z,Liu X,Ling M,Wang Q,Wang Q,Lu L,Shi L,Liu Y,Liu Q,Zhang A

    更新日期:2017-06-01 00:00:00

  • Genetic variations in the transforming growth factor-beta pathway as predictors of survival in advanced non-small cell lung cancer.

    abstract::The magnitude of benefit is variable for advanced non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy. The purpose of this study is to determine whether genetic variations in the transforming growth factor-beta (TGF-β) pathway are associated with clinical outcomes in NSCLC patients receiv...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr067

    authors: Lin M,Stewart DJ,Spitz MR,Hildebrandt MA,Lu C,Lin J,Gu J,Huang M,Lippman SM,Wu X

    更新日期:2011-07-01 00:00:00

  • A comparative electron microscope study of early changes in rat liver induced by N-nitrosopiperidine and 2,2',6,6'-tetramethyl-N-nitrosopiperidine.

    abstract::Inbred male Leeds rats were administered either the liver carcinogen N-nitrosopiperidine or the non-carcinogen 2,2',6,6'-tetramethyl-N-nitrosopiperidine in their drinking water at a concentration of 0.02%. Treatment was continued until the animals were killed, at 12 or 28 days, when their hepatic tissues were removed ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/2.5.385

    authors: Flaks B,Challis BC

    更新日期:1981-01-01 00:00:00

  • Metabolic activation of benzo[a]pyrene by a human hepatoma cell line.

    abstract::The liver-derived human cell line, Hep G2, has high benzo[a]pyrene-metabolizing activity and converts benzo[a]pyrene to intermediates that are mutagenic and that bind to DNA. This cell line will be useful for studying metabolic activation of polycyclic aromatic hydrocarbons and other xenobiotics by human tissue and as...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/1.10.871

    authors: Diamond L,Kruszewski F,Aden DP,Knowles BB,Baird WM

    更新日期:1980-01-01 00:00:00

  • Carcinogenic polycyclic aromatic hydrocarbons increase intracellular Ca2+ and cell proliferation in primary human mammary epithelial cells.

    abstract::Previous studies have shown that polycyclic aromatic hydrocarbons (PAHs) mobilize intracellular Ca2+ in human T cells by inositol trisphosphate-dependent mechanisms resulting from activation of phospholipase C-gamma by SRC-related protein tyrosine kinases, thereby mimicking antigen-receptor activation. Ca2+ appears to...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/18.6.1177

    authors: Tannheimer SL,Barton SL,Ethier SP,Burchiel SW

    更新日期:1997-06-01 00:00:00

  • Benzo[a]pyrene metabolites: formation in rat liver cell-culture lines, binding to macromolecules, and mutagenesis in V79 hamster cells.

    abstract::Benzo(a]pyrene was metabolized in liver cell lines derived from BC-IV and BD-IV rats which included several chemically-transformed lines (IAR-6-1; IAR-19; IAR-28), one spontaneous transformant (IAR-27) as well as one non-malignant line (IAR-20). Cultures were treated with tritiated benzo[a]pyrene over a 5-day period. ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/3.6.635

    authors: Selkirk JK,MacLeod MC,Kuroki T,Drevon C,Piccoli C,Montesano R

    更新日期:1982-01-01 00:00:00

  • Effect of vitamin C supplementation on gastric mucosal DNA damage.

    abstract::The effect of oral vitamin C supplementation on intragastric ascorbate levels and gastric mucosal DNA damage as measured by the 32P-postlabelling assay was assessed in 43 patients. In patients with normal gastric mucosa, treatment with vitamin C resulted in elevation of intragastric ascorbate levels in all cases. In t...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.2.291

    authors: Dyke GW,Craven JL,Hall R,Garner RC

    更新日期:1994-02-01 00:00:00

  • Alkenyl group is responsible for the disruption of microtubule network formation in human colon cancer cell line HT-29 cells.

    abstract::Alk(en)yl trisulfides (R-SSS-R') are organosulfur compounds produced by crushed garlic and other Allium vegetables. We found that these compounds exhibit potent anticancer effects through the reaction with microtubules, causing cell cycle arrest. Nine alk(en)yl trisulfides including dimethyl trisulfide, diethyl trisul...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgn124

    authors: Hosono T,Hosono-Fukao T,Inada K,Tanaka R,Yamada H,Iitsuka Y,Seki T,Hasegawa I,Ariga T

    更新日期:2008-07-01 00:00:00

  • Modulation of small G protein isoprenylation by anticancer monoterpenes in in situ mammary gland epithelial cells.

    abstract::Monoterpenes have been shown to both prevent and treat mammary cancer in animal models and are currently in clinical testing in advanced cancer patients. In this study, we investigated a biochemical modulation associated with the antitumor activity of monoterpenes, the inhibition of protein isoprenylation in monoterpe...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/19.5.827

    authors: Ren Z,Gould MN

    更新日期:1998-05-01 00:00:00

  • Rearrangements in minisatellite sequences induced by aflatoxin B1 in a metabolically competent strain of Saccharomyces cerevisiae.

    abstract::The role of aflatoxin B1 (AFB1) in the induction of rearrangements affecting minisatellite sequences was studied in an in vitro yeast model. The Saccharomyces cerevisiae strain used expresses human cytochrome P450 1A2 and NADPH-cytochrome P450 oxidoreductase and has previously been used to study genetic recombination ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/19.9.1673

    authors: Kaplanski C,Wild CP,Sengstag C

    更新日期:1998-09-01 00:00:00

  • Altered tRNA methylation in rats and mice fed lipotrope-deficient diets.

    abstract::A diet that is deficient in methionine, choline, folic acid and vitamin B12 has been found to induce alterations rapidly in liver tRNA methylation in male Fischer rats. In vitro assays indicated that activity of N2-guanine tRNA methyltransferase II (NMG2) was increased to 150% of controls levels in 1 week and 300% of ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/7.3.473

    authors: Wainfan E,Dizik M,Hluboky M,Balis ME

    更新日期:1986-03-01 00:00:00

  • Polymorphisms in predicted microRNA-binding sites in integrin genes and breast cancer: ITGB4 as prognostic marker.

    abstract::Integrins control the cell attachment to the extracellular matrix and play an important role in mediating cell proliferation, migration and survival. A number of important cancer-associated integrin genes can be regulated by microRNAs (miRNAs) that bind to their target sites in the 3' untranslated regions. We examined...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgn126

    authors: Brendle A,Lei H,Brandt A,Johansson R,Enquist K,Henriksson R,Hemminki K,Lenner P,Försti A

    更新日期:2008-07-01 00:00:00

  • Lycopene synergistically enhances quinacrine action to inhibit Wnt-TCF signaling in breast cancer cells through APC.

    abstract::We previously reported that quinacrine (QC) has anticancer activity against breast cancer cells. Here, we examine the mechanism of action of QC and its ability to inhibit Wnt-TCF signaling in two independent breast cancer cell lines. QC altered Wnt-TCF signaling components by increasing the levels of adenomatous polyp...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgs351

    authors: Preet R,Mohapatra P,Das D,Satapathy SR,Choudhuri T,Wyatt MD,Kundu CN

    更新日期:2013-02-01 00:00:00

  • Carnosol, an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-kappaB in mouse macrophages.

    abstract::Carnosol is a naturally occurring phytopolyphenol found in rosemary. Carnosol functions as antioxidant and anticarcinogen. In the present study, we compared the antioxidant activity of carnosol and other compounds extracted from rosemary. Carnosol showed potent antioxidative activity in alpha,alpha-diphenyl-beta-picry...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/23.6.983

    authors: Lo AH,Liang YC,Lin-Shiau SY,Ho CT,Lin JK

    更新日期:2002-06-01 00:00:00

  • DNA adduct formation and unscheduled DNA synthesis in rat esophagus in vivo after treatment with N-methyl-N-nitrosourea.

    abstract::An in vivo method for assessment of DNA adduct formation and unscheduled DNA synthesis (UDS) in the esophagus of rats was devised. Small ventral incisions were made in the neck and upper abdomen regions of 6 week old F344 rats and ligation of the esophagus with thread at the two extreme ends performed to make an esoph...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.2.235

    authors: Qin XS,Nakatsuru Y,Kohyama K,Ishikawa T

    更新日期:1990-02-01 00:00:00

  • The COX-2 inhibitor nimesulide suppresses superoxide and 8-hydroxy-deoxyguanosine formation, and stimulates apoptosis in mucosa during early colonic inflammation in rats.

    abstract::As we have shown previously [Tardieu,D., Jaeg,J.P., Cadet,J., Embvani,E., Corpet,D.E. and Petit,C. (1998) Cancer Lett, 134, 1-5], a 48-h treatment of 6% dextran sodium sulphate (DSS) in drinking water led to a reproducible 2-fold increase of the mutagenic oxidative lesion 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/21.5.973

    authors: Tardieu D,Jaeg JP,Deloly A,Corpet DE,Cadet J,Petit CR

    更新日期:2000-05-01 00:00:00

  • Poly (ADP-ribose) is not involved in the rejoining of DNA breaks accumulated to high levels in u.v.-irradiated HeLa cells.

    abstract::U.v. damage to the DNA of HeLa cells induces the polymerisation of ADP-ribose, but only if repair synthesis is inhibited so that incomplete repair sites (i.e., DNA breaks) accumulate to abnormally high levels. 3-Aminobenzamide greatly reduces the ADP-ribose polymerisation response. However, 3-aminobenzamide does not r...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/6.7.1033

    authors: Collins A

    更新日期:1985-07-01 00:00:00

  • Acetaldehyde alters proliferation, differentiation and adhesion properties of human colon adenocarcinoma cell line Caco-2.

    abstract::Studies with experimental animals indicate that acetaldehyde, the first metabolite of ethanol that is microbially formed in the colonic lumen, may play a role in ethanol-associated colorectal co-carcinogenesis. Although intracoIonic acetaldehyde concentrations are highest during the metabolism of exogenous ethanol, so...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/19.11.2031

    authors: Koivisto T,Salaspuro M

    更新日期:1998-11-01 00:00:00

  • Induction and repair inhibition of oxidative DNA damage by nickel(II) and cadmium(II) in mammalian cells.

    abstract::Compounds of nickel(II) and cadmium(II) are carcinogenic to humans and to experimental animals. One frequently discussed mechanism involved in tumor formation is an increase in reactive oxygen species by both metals with the subsequent generation of oxidative DNA damage. In the present study we used human HeLa cells t...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/18.5.1021

    authors: Dally H,Hartwig A

    更新日期:1997-05-01 00:00:00

  • Characterization of the mutational profile of (+)-7R,8S-dihydroxy-9S, 10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene at the hypoxanthine (guanine) phosphoribosyltransferase gene in repair-deficient Chinese hamster V-H1 cells.

    abstract::Earlier studies have shown that the profile of mutations induced by (+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (+)-BPDE at the hypoxanthine (guanine) phosphoribosyltransferase (hprt) gene of Chinese hamster V79 cells was dependent on the concentration of (+)-BPDE. In the present study, we exami...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/20.12.2279

    authors: Schiltz M,Cui XX,Lu YP,Yagi H,Jerina DM,Zdzienicka MZ,Chang RL,Conney AH,Wei SJ

    更新日期:1999-12-01 00:00:00

  • Prevalence of HPV Infection in Racial-Ethnic Subgroups of Head and Neck Cancer Patients.

    abstract::The landscape of HPV infection in racial/ethnic subgroups of head and neck cancer (HNC) patients has not been evaluated carefully. In this study, a meta-analysis examined the prevalence of HPV in HNC patients of African ancestry. Additionally, a pooled analysis of subject-level data was also performed to investigate H...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgw203

    authors: Ragin C,Liu JC,Jones G,Shoyele O,Sowunmi B,Kennett R,Groen HJ,Gibbs D,Blackman E,Esan M,Brandwein MS,Devarajan K,Bussu F,Chernock R,Chien CY,Cohen MA,Samir EM,Mikio S,D'Souza G,Funchain P,Eng C,Gollin SM,Hong

    更新日期:2017-02-01 00:00:00

  • Induction of DMBT1 expression by reduced ERK activity during a gastric mucosa differentiation-like process and its association with human gastric cancer.

    abstract::Abnormalities in the expression of DMBT1 (deleted in malignant brain tumors 1) have been implicated in the development of esophageal, gastric and colorectal cancers of the alimentary tract, but the underlying mechanism remains unclear. In the present study, using the gastric cell line AGS, we identified two intracellu...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgi045

    authors: Kang W,Nielsen O,Fenger C,Leslie G,Holmskov U,Reid KB

    更新日期:2005-06-01 00:00:00

  • Inhibition of 7,12-dimethylbenz[a]anthracene-induced genotoxicity in Chinese hamster ovary cells by retinol and retinoic acid.

    abstract::The effects of retinol and retinoic acid on cytotoxicity and mutation expression at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in Chinese hamster ovary (CHO) cells with or without exogenous metabolic activation were studied in the presence and absence of known chemical mutagens. Neither retinol ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/9.7.1307

    authors: Budroe JD,Schol HM,Shaddock JG,Casciano DA

    更新日期:1988-07-01 00:00:00

  • Nafenopin-induced rat liver peroxisome proliferation reduces DNA methylation by N-nitrosodimethylamine in vivo.

    abstract::The hypolipidaemic drug nafenopin (NAF) has been shown to enhance the hepatocarcinogenic effect of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine in rats. We have investigated whether the NAF-induced peroxisome proliferation in hepatocytes interferes with NDMA's metabolism and interaction with DNA. Adult male...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/6.9.1309

    authors: Wiestler OD,Schmerold I,Fringes B,Volk B,Kleihues P

    更新日期:1985-09-01 00:00:00

  • Dose-response studies of MeIQx in rat liver and liver DNA at low doses.

    abstract::2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a heterocyclic amine mutagen found in cooked meats and is carcinogenic in mice and rats at high doses (mg/kg body wt). Humans, however, are exposed to low amounts (p.p.b.) in the diet, and the effects caused by exposure to human equivalent doses of MeIQx have be...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/16.2.367

    authors: Frantz CE,Bangerter C,Fultz E,Mayer KM,Vogel JS,Turteltaub KW

    更新日期:1995-02-01 00:00:00

  • Expression of transforming growth factor alpha/epidermal growth factor receptor, hepatocyte growth factor/c-met and acidic fibroblast growth factor/fibroblast growth factor receptors during hepatocarcinogenesis.

    abstract::It is widely believed that abnormal production of polypeptide growth factors, together with other molecular alterations, play an important role in neoplastic development. Transforming growth factor alpha (TGFalpha), hepatocyte growth factor (HGF) and acidic fibroblast growth factor (aFGF) are the three major growth fa...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.5.931

    authors: Hu Z,Evarts RP,Fujio K,Omori N,Omori M,Marsden ER,Thorgeirsson SS

    更新日期:1996-05-01 00:00:00

  • Foreign compound metabolism capacity in man measured from metabolites of dietary caffeine.

    abstract::Caffeine is sequentially metabolized by cytochrome P4501A2 (CYP1A2), N-acetyltransferase (NAT) and/or xanthine oxidase (XO). In the present study the activity of these three enzymes was estimated from ratios of the metabolites formed from dietary caffeine and excreted into the urine collected as spot samples. In the u...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/13.9.1561

    authors: Vistisen K,Poulsen HE,Loft S

    更新日期:1992-09-01 00:00:00

  • Binding of benzo[a]pyrene metabolites in the rat intestinal lumen by magnetic polyethyleneimine microcapsules following an intragastric dose of [14C]benzo[a]pyrene.

    abstract::Semi-permeable magnetic polyethyleneimine (PEI) microcapsules have been developed to trap carcinogens and their metabolites in vivo and their time-dependent binding of a model carcinogen, [14C]benzo[a]pyrene [( 14C]BaP), is studied within the intestinal lumen. Overall, approximately 0.5% of an intragastric BaP dose wa...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/8.6.825

    authors: Povey AC,Brouet I,Bartsch H,O'Neill IK

    更新日期:1987-06-01 00:00:00

  • Sulforaphane and its glutathione conjugate but not sulforaphane nitrile induce UDP-glucuronosyl transferase (UGT1A1) and glutathione transferase (GSTA1) in cultured cells.

    abstract::Glucoraphanin in Brassica vegetables breaks down to either sulforaphane or sulforaphane nitrile depending on the conditions, and sulforaphane can be further conjugated with glutathione. Using a high-throughput microtitre plate assay and TaqMan real time quantitative RT-PCR to measure mRNA, we show that sulforaphane an...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/23.8.1399

    authors: Basten GP,Bao Y,Williamson G

    更新日期:2002-08-01 00:00:00

  • Interactions among genes, tumor biology and the environment in cancer health disparities: examining the evidence on a national and global scale.

    abstract::Cancer incidence and mortality rates show great variations across nations and between population groups. These variations are largely explained by differences in age distribution, diet and lifestyle, access to health care, cultural barriers and exposure to carcinogens and pathogens. Cancers caused by infections are si...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1093/carcin/bgr066

    authors: Wallace TA,Martin DN,Ambs S

    更新日期:2011-08-01 00:00:00