NMDA antagonist inhibits the extracellular signal-regulated kinase pathway and suppresses cancer growth
| العنوان: | NMDA antagonist inhibits the extracellular signal-regulated kinase pathway and suppresses cancer growth |
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| المؤلفون: | Christoph Bührer, Elena E. Pohl, Alexander Gratopp, Wojciech Rzeski, Petra Bittigau, Lechoslaw Turski, Marco Sifringer, Chrysanthy Ikonomidou, Henrik H. Hansen, Ursula Felderhoff-Mueser, Marta Stryjecka-Zimmer, Angela M. Kaindl, Andrzej Stepulak, Stefanie Endesfelder |
| المصدر: | Proceedings of the National Academy of Sciences. 102:15605-15610 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Cyclin-Dependent Kinase Inhibitor p21, Lung Neoplasms, MAP Kinase Signaling System, Antineoplastic Agents, Biology, Fibroblast growth factor, Receptors, N-Methyl-D-Aspartate, Cyclin D1, Extracellular, medicine, Humans, Phosphorylation, Cyclic AMP Response Element-Binding Protein, Extracellular Signal-Regulated MAP Kinases, Cells, Cultured, Cell Proliferation, Multidisciplinary, Kinase, Cell growth, Biological Sciences, Cell cycle, Dizocilpine, Gene Expression Regulation, Cancer cell, Cancer research, Dizocilpine Maleate, Excitatory Amino Acid Antagonists, medicine.drug |
| الوصف: | Glutamate antagonists limit the growth of human cancers in vitro . The mechanism of anticancer action of NMDA antagonists is not known, however. In this article, we report that the NMDA antagonist dizocilpine inhibits the extracellular signal-regulated kinase 1/2 pathway, an intracellular signaling cascade that is activated by growth factors and controls the proliferation of cancer cells. Dizocilpine reduces the phosphorylation of cAMP-responsive element binding protein, suppresses the expression of cyclin D1, up-regulates the cell cycle regulators and tumor suppressor proteins p21 and p53, and increases the number of lung adenocarcinoma cells in the G 2 and S phases of the cell cycle. Silencing of the tumor suppressor protein p21 abolishes antiproliferative action of dizocilpine. Consistent with inhibition of the extracellular signal-regulated kinase 1/2-signaling cascade, dizocilpine reverses the stimulation of proliferation induced by epidermal, insulin, and basic fibroblast growth factors in lung adenocarcinoma cells. Furthermore, dizocilpine prolongs the survival of mice with metastatic lung adenocarcinoma and slows the growth of neuroblastoma and rhabdomyosarcoma in mice. These findings reveal the mechanism of antiproliferative action of dizocilpine and indicate that it may be useful in the therapy of human cancers. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8e0477001abdc95220b2a79d62686a07 https://doi.org/10.1073/pnas.0507679102 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8e0477001abdc95220b2a79d62686a07 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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