The effect of tyrphostins AG494 and AG1478 on the autocrine growth regulation of A549 and DU145 cells
| Autor: | Anna Adamczyk, Kinga Reichert, Janusz Ligeza, Agnieszka Bojko, Joanna Ligęza, Andrzej Klein |
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| Rok vydání: | 2012 |
| Předmět: |
MAPK/ERK pathway
Histology Paclitaxel Cell Survival Tyrphostins Biology epidermal growth factor (EGF) Pathology and Forensic Medicine Inhibitory Concentration 50 DU145 Epidermal growth factor Cell Line Tumor Humans A549 cells lcsh:QH573-671 Phosphorylation Kinase activity Extracellular Signal-Regulated MAP Kinases Autocrine signalling Protein Kinase Inhibitors Protein kinase B DU145 cells Cell Proliferation Cell Death Dose-Response Relationship Drug lcsh:Cytology Cell growth autocrine growth regulation General Medicine epidermal growth factor receptor (EGFR) ErbB Receptors Autocrine Communication Quinazolines Cancer research sense organs tyrphostins Proto-Oncogene Proteins c-akt hormones hormone substitutes and hormone antagonists |
| Zdroj: | Folia Histochemica et Cytobiologica, Vol 50, Iss 2, Pp 186-195 (2012) |
| ISSN: | 1897-5631 0239-8508 |
| DOI: | 10.5603/fhc.2012.0028 |
| Popis: | We employed two selective EGFR tyrosine kinase inhibitors: AG494 (reversible) and AG1478 (irreversible) for growth regulation of human lung (A549) and prostate (DU145) cancer cell lines, cultured in chemically defined DMEM/F12 medium. Both tested tyrphostins significantly inhibited autocrine growth of the investigated cell lines. The action of AG494 was dose dependent, and at highest concentrations led to complete inhibition of growth. AG1478 seemed to be more effective at lower concentrations, but was unable to completely inhibit growth of A549 cells. Inhibition of EGFR kinase activity by AG494 in contrast to AG1478 had no effect on the activity of ERK in both cell lines. Both EGFR’s inhibitors induced apoptosis of the investigated lung and prostate cancer cell lines, but the proapoptotic effect of the investigated tyrphostins was greater in A549 than in DU145 cells. The tyrphostins arrested cell growth of DU145 and A549 cells in the G1 phase, similarly to other known inhibitors of EGFR. The influence of AG494 and AG1478 on the activity of two signaling proteins (AKT and ERK) was dependent upon the kind of investigated cells. In the case of DU145 cells, there was an evident decline in enzymatic activity of both kinases (stronger for AG1478), while in A549, only AG1478 effectively inhibited the phosphorylation of Akt. Tyrphostins AG494 and AG1478 are ATP-competitors and are supposed to have a similar mechanism of action, but our results suggest that this is not quite true. |
| Databáze: | OpenAIRE |
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