Proteomic Profiling of Germ Cell Cancer Cells Treated with Aaptamine, a Marine Alkaloid with Antiproliferative Activity

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• 作者：Sergey A. Dyshlovoy ; Ina Naeth ; Simone Venz ; Michael Preukschas ; Henning Sievert ; Christine Jacobsen ; Larisa K. Shubina ; Manuela Gesell Salazar ; Christian Scharf ; Reinhard Walther ; Marcel Krepstakies ; Poornima Priyadarshini ; Joachim Hauber ; Sergey N. Fedorov ; Carsten Bokemeyer ; Valentin A. Stonik ; Stefan Balabanov ; Friedemann Honecker
• 刊名：Journal of Proteome Research
• 出版年：2012
• 出版时间：April 6, 2012
• 年：2012
• 卷：11
• 期：4
• 页码：2316-2330
• 全文大小：692K
• 年卷期：v.11,no.4(April 6, 2012)
• ISSN：1535-3907

文摘

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 渭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.

Keywords:

aaptamine; marine alkaloids; antiproliferative activity; germ cell cancer; proteome analysis; eIF5A; hypusination; differentiation