Proteomic profiling of germ cell cancer cells treated with aaptamine, a marine alkaloid with antiproliferative activity
| Autor: | Sergey N. Fedorov, Poornima Priyadarshini, Simone Venz, Stefan Balabanov, Reinhard Walther, Henning Sievert, Ina Naeth, Marcel Krepstakies, Christian Scharf, Larisa K. Shubina, Friedemann Honecker, Christine Jacobsen, Manuela Gesell Salazar, Michael Preukschas, Valentin A. Stonik, Carsten Bokemeyer, Joachim Hauber, Sergey A. Dyshlovoy |
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| Přispěvatelé: | University of Zurich, Balabanov, S |
| Rok vydání: | 2012 |
| Předmět: |
Proteomics
1303 Biochemistry Aaptos aaptos Proteome Cell Survival Molecular Sequence Data 610 Medicine & health 1600 General Chemistry Antineoplastic Agents Biochemistry chemistry.chemical_compound Peptide Initiation Factors Eukaryotic initiation factor Cell Line Tumor Humans Electrophoresis Gel Two-Dimensional Amino Acid Sequence Naphthyridines Mode of action Cell Proliferation Hypusine Biological Products Oxidoreductases Acting on CH-NH Group Donors biology Dose-Response Relationship Drug Lysine Proteins RNA-Binding Proteins Reproducibility of Results General Chemistry Cell Cycle Checkpoints Cell cycle Neoplasms Germ Cell and Embryonal biology.organism_classification Molecular biology Cell biology HEK293 Cells chemistry Apoptosis Cell culture 10032 Clinic for Oncology and Hematology EIF5A |
| Zdroj: | Journal of proteome research. 11(4) |
| ISSN: | 1535-3907 |
| Popis: | Aaptamine is a marine compound isolated from the sponge Aaptos aaptos showing antiproliferative properties via an undefined mode of action. We analyzed the effects of aaptamine treatment on the proliferation and protein expression of the pluripotent human embryonal carcinoma cell line NT2. Effects on proliferation, cell cycle distribution, and induction of apoptosis were analyzed. At lower concentrations, including the IC50 of 50 μM, aaptamine treatment resulted in a G2/M phase cell cycle arrest, whereas at higher concentrations, induction of apoptosis was seen. Differentially expressed proteins were assessed by 2D-PAGE and mass spectrometry, followed by verification and analysis of protein modifications of the most significantly up- and down-regulated proteins. Aaptamine treatment at the IC50 for 48 h resulted in alteration of 10 proteins, of which five each showed up- and down-regulation. Changes in the 2D map were frequently noticed as a result of post-transcriptional modifications, e.g., of the hypusine modification of the eukaryotic initiation factor 5A (eIF5A). Observed alterations such as increased expression of CRABP2 and hypusination of eIF5A have previously been identified during differentiation of pluripotent cells. For the first time, we describe changes in protein expression caused by aaptamine, providing valuable information regarding the mode of action of this compound. |
| Databáze: | OpenAIRE |
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