Proteasome inhibition overcomes the resistance of renal cell carcinoma cells against the PPARγ ligand troglitazone
| Autor: | K von Schwarzenberg, Katharina M. Brauer, Peter Brossart, Anita Bringmann, A. Schaub, Stefanie Ae Held |
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| Rok vydání: | 2009 |
| Předmět: |
Proteasome Endopeptidase Complex
Programmed cell death Cell Antineoplastic Agents Apoptosis Biology Endoplasmic Reticulum Bortezomib Troglitazone Cellular and Molecular Neuroscience Cell Line Tumor medicine Humans Chromans Carcinoma Renal Cell Molecular Biology Pharmacology Caspase 3 NF-kappa B Drug Synergism Cell Biology Hypoxia-Inducible Factor 1 alpha Subunit Boronic Acids Kidney Neoplasms Cell biology PPAR gamma medicine.anatomical_structure Drug Resistance Neoplasm Cell culture Pyrazines Cancer research Proteasome inhibitor Cytokines Intercellular Signaling Peptides and Proteins Molecular Medicine Angiogenesis Inducing Agents Thiazolidinediones Mitogen-Activated Protein Kinases Signal transduction Proteasome Inhibitors Signal Transduction medicine.drug |
| Zdroj: | Cellular and Molecular Life Sciences. 66:1295-1308 |
| ISSN: | 1420-9071 1420-682X |
| DOI: | 10.1007/s00018-009-8542-7 |
| Popis: | In order to analyze the effects of peroxisome proliferator-activated receptor-gamma (PPARgamma) activation on renal cell carcinomas we utilized several cell lines that were treated with the high affinity PPARgamma agonist, troglitazone. Incubation of RCC cells with troglitazone resulted in reduced secretion of growth factors that was due to the inhibition of MAP kinase signaling and reduced nuclear localized expression of relB and HIF1alpha. Interestingly, the cell lines used showed a different sensitivity towards apoptosis induction that did not correlate with the inhibition of growth factors or expression of pro- and antiapoptotic molecules. To overcome this resistance the cells were treated with a combination of troglitazone and the proteasome inhibitor, bortezomib. The combination of both compounds induced apoptosis even in cells resistant to both agents alone, due to increased induction of ER-stress and caspase-3 mediated cell death. |
| Databáze: | OpenAIRE |
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