title: Proteomic profiling of germ cell cancer cells treated with aaptamine, a marine alkaloid with antiproliferative activity.
abstract: 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.
authors.affiliation: Department of Oncology, Haematology and Bone Marrow Transplantation, Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Dyshlovoy
authors.forename: Ina
authors.initials: I
authors.lastname: Naeth
authors.forename: Simone
authors.initials: S
authors.lastname: Venz
authors.forename: Michael
authors.initials: M
authors.lastname: Preukschas
authors.forename: Henning
authors.initials: H
authors.lastname: Sievert
authors.forename: Christine
authors.initials: C
authors.lastname: Jacobsen
authors.forename: Larisa K
authors.initials: LK
authors.lastname: Shubina
authors.forename: Manuela
authors.initials: M
authors.lastname: Gesell Salazar
authors.forename: Christian
authors.initials: C
authors.lastname: Scharf
authors.forename: Reinhard
authors.initials: R
authors.lastname: Walther
authors.forename: Marcel
authors.initials: M
authors.lastname: Krepstakies
authors.forename: Poornima
authors.initials: P
authors.lastname: Priyadarshini
authors.forename: Joachim
authors.initials: J
authors.lastname: Hauber
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Fedorov
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Valentin A
authors.initials: VA
authors.lastname: Stonik
authors.forename: Stefan
authors.initials: S
authors.lastname: Balabanov
authors.forename: Friedemann
authors.initials: F
authors.lastname: Honecker
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008969:Molecular Sequence Data; D009287:Naphthyridines / Q000494:pharmacology*; D009373:Neoplasms, Germ Cell and Embryonal / Q000737:chemistry* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000378:metabolism; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000032:analysis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D016601:RNA-Binding Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D008239:Lysine; D009287:Naphthyridines; D000587:Oxidoreductases Acting on CH-NH Group Donors; D010448:Peptide Initiation Factors; D011506:Proteins; D020543:Proteome; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C100028:hypusine; C063507:deoxyhypusine synthase; C043986:aaptamine