Proteomic profiling of germ cell cancer cells treated with aaptamine, a marine alkaloid with antiproliferative activity.
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Proteomic profiling of germ cell cancer cells treated with aaptamine, a marine alkaloid with antiproliferative activity. / Dyshlovoy, Sergey A.; Naeth, Ina; Venz, Simone; Preukschas, Michael; Sievert, Henning; Jacobsen, Christine; Shubina, Larisa K; Manuela, Gesell Salazar; Scharf, Christian; Walther, Reinhard; Krepstakies, Marcel; Priyadarshini, Poornima; Hauber, Joachim; Fedorov, Sergey N; Bokemeyer, Carsten; Stonik, Valentin A; Balabanov, Stefan; Honecker, Friedemann.
In: J PROTEOME RES, Vol. 11, No. 4, 4, 2012, p. 2316-2330.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Proteomic profiling of germ cell cancer cells treated with aaptamine, a marine alkaloid with antiproliferative activity.
AU - Dyshlovoy, Sergey A.
AU - Naeth, Ina
AU - Venz, Simone
AU - Preukschas, Michael
AU - Sievert, Henning
AU - Jacobsen, Christine
AU - Shubina, Larisa K
AU - Manuela, Gesell Salazar
AU - Scharf, Christian
AU - Walther, Reinhard
AU - Krepstakies, Marcel
AU - Priyadarshini, Poornima
AU - Hauber, Joachim
AU - Fedorov, Sergey N
AU - Bokemeyer, Carsten
AU - Stonik, Valentin A
AU - Balabanov, Stefan
AU - Honecker, Friedemann
PY - 2012
Y1 - 2012
N2 - 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 ?M, 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.
AB - 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 ?M, 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.
KW - Humans
KW - Reproducibility of Results
KW - Cell Line, Tumor
KW - Amino Acid Sequence
KW - Molecular Sequence Data
KW - Dose-Response Relationship, Drug
KW - HEK293 Cells
KW - Cell Proliferation/drug effects
KW - Cell Survival/drug effects
KW - Proteomics/methods
KW - Electrophoresis, Gel, Two-Dimensional
KW - Lysine/analogs & derivatives/metabolism
KW - Antineoplastic Agents/pharmacology
KW - Peptide Initiation Factors/metabolism
KW - RNA-Binding Proteins/metabolism
KW - Cell Cycle Checkpoints/drug effects
KW - Biological Agents/pharmacology
KW - Naphthyridines/pharmacology
KW - Neoplasms, Germ Cell and Embryonal/chemistry/drug therapy/metabolism/pathology
KW - Oxidoreductases Acting on CH-NH Group Donors/genetics/metabolism
KW - Proteins/analysis/genetics/metabolism
KW - Proteome/analysis/drug effects/genetics/metabolism
KW - Humans
KW - Reproducibility of Results
KW - Cell Line, Tumor
KW - Amino Acid Sequence
KW - Molecular Sequence Data
KW - Dose-Response Relationship, Drug
KW - HEK293 Cells
KW - Cell Proliferation/drug effects
KW - Cell Survival/drug effects
KW - Proteomics/methods
KW - Electrophoresis, Gel, Two-Dimensional
KW - Lysine/analogs & derivatives/metabolism
KW - Antineoplastic Agents/pharmacology
KW - Peptide Initiation Factors/metabolism
KW - RNA-Binding Proteins/metabolism
KW - Cell Cycle Checkpoints/drug effects
KW - Biological Agents/pharmacology
KW - Naphthyridines/pharmacology
KW - Neoplasms, Germ Cell and Embryonal/chemistry/drug therapy/metabolism/pathology
KW - Oxidoreductases Acting on CH-NH Group Donors/genetics/metabolism
KW - Proteins/analysis/genetics/metabolism
KW - Proteome/analysis/drug effects/genetics/metabolism
M3 - SCORING: Journal article
VL - 11
SP - 2316
EP - 2330
JO - J PROTEOME RES
JF - J PROTEOME RES
SN - 1535-3893
IS - 4
M1 - 4
ER -
