Effects of statins and farnesyl transferase inhibitors on ERK phosphorylation, apoptosis and cell viability in non-small lung cancer cells
| Autor: | Alessandro Vatrella, Mt Busceti, Luca Gallelli, Daniela Falcone, Michele Caraglia, Rosa Terracciano, Rosario Maselli, G. Pelaia, Teresa Renda, D. Fratto, Rocco Savino |
|---|---|
| Přispěvatelé: | Pelaia, G, Gallelli, L, Renda, T, Fratto, D, Falcone, D, Caraglia, Michele, Busceti, Mt, Terracciano, R, Vatrella, A, Maselli, R, Savino, R. |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
MAPK/ERK pathway
Simvastatin Lung Neoplasms farnesyl transferase inhibitors ERK apoptosis statins non-small lung cancer cells Cell Survival MAP Kinase Signaling System Cell Antineoplastic Agents Apoptosis Biology Quinolones Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Farnesyltranstransferase Humans Viability assay Phosphorylation Extracellular Signal-Regulated MAP Kinases Lung TUNEL assay Kinase Caspase 3 Farnesyl Transferase Inhibitor Cell Biology General Medicine Original Articles Molecular biology Enzyme Activation medicine.anatomical_structure Cancer research Hydroxymethylglutaryl-CoA Reductase Inhibitors Intracellular |
| Popis: | Objective 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) can affect post-translational processes, thus being responsible for decreased farnesylation and geranylgeranylation of intracellular small G proteins such as Ras, Rho and Rac, essential for cell survival and proliferation. In this regard, recent in vitro and in vivo studies suggest a possible role for both statins and farnesyl transferase inhibitors in the treatment of malignancies. Within such a context, the aim of our study was to investigate effects of either simvastatin (at concentrations of 1, 15, and 30 μm) or the farnesyl transferase inhibitor R115777 (at concentrations of 0.1, 1, and 10 μm), on two cultures of human non-small lung cancer cells, adenocarcinoma (GLC-82) and squamous (CALU-1) cell lines. In particular, we evaluated actions of these two drugs on phosphorylation of the ERK1/2 group of mitogen-activated protein kinases and on apoptosis, plus on cell numbers and morphology. Materials and Methods Western blotting was used to detect ERK phosphorylation, and to assess apoptosis by evaluating caspase-3 activation; apoptosis was also further assessed by terminal deoxynucleotidyl-mediated dUTP nick end labelling (TUNEL) assay. Cell counting was performed after trypan blue staining. Results and conclusion In both GLC-82 and CALU-1 cell lines, simvastatin and R115777 significantly reduced ERK phosphorylation; this effect, which reached the greatest intensity after 36 h treatment, was paralleled by a concomitant induction of apoptosis, documented by significant increase in both caspase-3 activation and TUNEL-positive cells, associated with a reduction in cell numbers. Our results thus suggest that simvastatin and R115777 may exert, in susceptible lung cancer cell phenotypes, a pro-apoptotic and anti-proliferative activity, which appears to be mediated by inhibition of the Ras/Raf/MEK/ERK signalling cascade. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|