Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Pharmacoproteomic study of the natural product Ebenfuran III in DU-145 prostate cancer cells: The quantitative and temporal interrogation of chemically induced cell death at the protein level
Δημιουργός/Συγγραφέας:	Roumeliotis T.I. Halabalaki M. Alexi X. Ankrett D. Giannopoulou E.G. Skaltsounis A.-L. Sayan B.S. [EL] Αλέξης, Μιχαήλ Ν.[EN] Alexis, Michael N. Townsend P.A. Garbis S.D.
Ημερομηνία:	2013
Γλώσσα:	Αγγλικά
ISSN:	1535-3893
DOI:	10.1021/pr300968q
Άλλο:	PubMed ID: 23418717
Περίληψη:	A naturally occurring benzofuran derivative, Ebenfuran III (Eb III), was investigated for its antiproliferative effects using the DU-145 prostate cell line. Eb III was isolated from Onobrychis ebenoides of the Leguminosae family, a plant endemic in Central and Southern Greece. We have previously reported that Eb III exerts significant cytotoxic effects on certain cancer cell lines. This effect is thought to occur via the isoprenyl moiety at the C-5 position of the molecule. The study aim was to gain a deeper understanding of the pharmacological effect of Eb III on DU-145 cell death at the translational level using a relative quantitative and temporal proteomics approach. Proteins extracted from the cell pellets were subjected to solution phase trypsin proteolysis followed by iTRAQ-labeling. The labeled tryptic peptide extracts were then fractionated using strong cation exchange chromatography and the fractions were analyzed by nanoflow reverse phase ultraperformance liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry analysis using a hybrid QqTOF platform. Using this approach, we compared the expression levels of 1360 proteins analyzed at ≤1% global protein false discovery rate (FDR), commonly present in untreated (control, vehicle only) and Eb III-treated cells at the different exposure time points. Through the iterative use of Ingenuity Pathway Analysis with hierarchical clustering of protein expression patterns, followed by bibliographic research, the temporal regulation of the Calpain-1, ERK2, PAR-4, RAB-7, and Bap31 proteins were identified as potential nodes of multipathway convergence to Eb III induced DU-145 cell death. These proteins were further verified with Western blot analysis. This gel-free, quantitative 2DLC-MS/MS proteomics method effectively captured novel modulated proteins in the DU-145 cell line as a response to Eb III treatment. This approach also provided greater insight to the multifocal and combinatorial signaling pathways implicated in Eb III-induced cell death.
Τίτλος πηγής δημοσίευσης:	Journal of Proteome Research
Τόμος/Κεφάλαιο:	12
Τεύχος:	4
Σελίδες:	1591-1603
Θεματική Κατηγορία:	[EL] Θεραπευτική. Φαρμακολογία[EN] Therapeutics.Pharmacology [EL] Βιοχημεία[EN] Biochemistry
Λέξεις-Κλειδιά:	DU-145 prostate cancer cells Ebenfuran III
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2013 American Chemical Society.
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο