Document Detail

New Molecular Markers for Prostate Tumor Imaging: A Study on 2-Methylene Substituted Fatty Acids as New AMACR Inhibitors.
MedLine Citation:
PMID:  21812041     Owner:  NLM     Status:  Publisher    
The development of prostate carcinoma is associated with alterations in fatty acid metabolism. α-Methylacyl-CoA racemase (AMACR) is a peroxisomal and mitochondrial enzyme that catalyses interconversion between the (S)/(R)-isomers of a range of α-methylacyl-CoA thioesters. AMACR is involved in the β-oxidation of the dietary branched-chain fatty acids and bile acid intermediates. It is highly expressed in prostate (more than 95 %), colon (92 %), and breast cancers (44 %) but not in the respective normal or hyperplastic tissues. Thus, targeting of AMACR could be a new strategy for molecular imaging and therapy of prostate and some other cancers. Unlabeled 2-methylenacyl-CoA thioesters (12 a-c) were designed as AMACR binding ligands. The thioesters were tested for their ability to inhibit the AMACR-mediated epimerization of (25R)-THC-CoA and were found to be strong AMACR inhibitors. Radioiodinated (E)-(131) I-13-iodo-2-methylentridec-12-enoic acid ((131) I-7 c) demonstrated preferential retention in AMACR-positive prostate tumor cells (LNCaP, LNCaP C4-2wt and DU145) compared with both AMACR-knockout LNCaP C4-2 AMACR-siRNA and benign BPH1 prostate cell lines. A significant protein-bound radioactive fraction with main bands at 47 (sum of molecular weights of AMACR plus 12 c), 70, and 75 kDa was detected in LNCaP C4-2 wt cells. In contrast, only negligible amounts of protein-bound radioactivity were found in LNCaP C4-2 AMACR-siRNA cells.
Agnieszka Morgenroth; Elizaveta A Urusova; Cornelia Dinger; Ehab Al-Momani; Thomas Kull; Gerhard Glatting; Holm Frauendorf; Olaf Jahn; Felix M Mottaghy; Sven N Reske; Boris D Zlatopolskiy
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-2
Journal Detail:
Title:  Chemistry (Weinheim an der Bergstrasse, Germany)     Volume:  -     ISSN:  1521-3765     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9513783     Medline TA:  Chemistry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Klinik für Nuklearmedizin, Aachen University, RWTH, Pauwelsstr. 30, 52074 Aachen (Germany), Fax: (+49) 241-80-82520; Klinik für Nuklearmedizin, Ulm University, Albert-Einstein-Allee 23, 89081 Ulm (Germany).
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