Adenine nucleotides inhibit proliferation of the human lung adenocarcinoma cell line LXF-289 by activation of nuclear factor kappaB1 and mitogen-activated protein kinase pathways
| Autor: | Tobias Welte, Fariba Sedehizade, Roland Hartig, Rainer Schäfer, Georg Reiser |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Lung Neoplasms
Antineoplastic Agents Mitogen-activated protein kinase kinase Adenocarcinoma Biochemistry Adenosine Triphosphate Cell Line Tumor Humans Integrin-linked kinase ASK1 Molecular Biology Protein kinase B Cell Proliferation MAP kinase kinase kinase biology Receptors Purinergic P2 Cyclin-dependent kinase 2 Cell Cycle NF-kappa B p50 Subunit Drug Synergism Cell Biology Molecular biology Cell biology Up-Regulation Adenosine Diphosphate biology.protein Cyclin-dependent kinase 9 Mitogen-Activated Protein Kinases Platelet-derived growth factor receptor Signal Transduction |
| Zdroj: | The FEBS journal. 273(16) |
| ISSN: | 1742-464X |
| Popis: | Extracellular nucleotides have a profound role in the regulation of the proliferation of diseased tissue. We studied how extracellular nucleotides regulate the proliferation of LXF-289 cells, the adenocarcinoma-derived cell line from human lung bronchial tumor. ATP and ADP strongly inhibited LXF-289 cell proliferation. The nucleotide potency profile was ATP = ADP = ATPgammaS > > UTP, UDP, whereas alpha,beta-methylene-ATP, beta,gamma-methylene-ATP, 2',3'-O-(4-benzoylbenzoyl)-ATP, AMP and UMP were inactive. The nucleotide potency profile and the total blockade of the ATP-mediated inhibitory effect by the phospholipase C inhibitor U-73122 clearly show that P2Y receptors, but not P2X receptors, control LXF-289 cell proliferation. Treatment of proliferating LXF-289 cells with 100 microm ATP or ADP induced significant reduction of cell number and massive accumulation of cells in the S phase. Arrest in S phase is also indicated by the enhancement of the antiproliferative effect of ATP by coapplication of the cytostatic drugs cisplatin, paclitaxel and etoposide. Inhibition of LXF-289 cell proliferation by ATP was completely reversed by inhibitors of extracellular signal related kinase-activating kinase/extracellular signal related kinase 1/2 (PD98059, U0126), p38 mitogen-activated protein kinase (SB203508), phosphatidylinositol-3-kinase (wortmannin), and nuclear factor kappaB1 (SN50). Western blot analysis revealed transient activation of p38 mitogen-activated protein kinase, extracellular signal-related kinase 1/2, and nuclear factor kappaB1 and possibly new formation of p50 from its precursor p105. ATP-induced attenuation of LXF-289 cell proliferation was accompanied by transient translocation of p50 nuclear factor kappaB1 and extracellular signal-related kinase 1/2 to the nucleus in a similar time period. In summary, inhibition of LXF-289 cell proliferation is mediated via P2Y receptors by activation of multiple mitogen-activated protein kinase pathways and nuclear factor kappaB1, arresting the cells in the S phase. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text