| N6-isopentenyladenosine arrests tumor cell proliferation by inhibiting farnesyl diphosphate synthase and protein prenylation. | |
| | |
MedLine Citation:
|
PMID: 16507758 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The physiological effects of a variety of N6-substituted adenine and adenosine derivatives called cytokinins have been documented in plants, but information on their occurrence and function in other biological system is limited. Here we investigated the anti-proliferative effect of N6-isopentenyladenosine (i6A), an adenosine and isoprenoid derivative, in a thyroid cell system, FRTL-5 wild-type, and K-ras transformed KiMol cells. Addition of i6A to FRTL-5 cells caused a dose-dependent arrest of the G0-G1 cell phase transition associated with a reduction of cells in the S phase that was much more evident in KiMol cells. I6A arrested tumor cell proliferation by inhibiting farnesyl diphosphate synthase (FPPS) and protein prenylation. Indeed the addition of farnesol reversed these effects and i6A affected protein prenylation, in particular lamin B processing. I6A effect was not mediated by the adenosine receptor but was due to a direct modulation of FPPS enzyme activity as a result of its uptake inside the cells. I6A inhibited FPPS activity more efficaciously in KiMol cells than in normal FRTL-5. Moreover, the i6A anti-proliferative effect was evaluated in vivo in a nude mouse xenograft model, where KiMol cells were implanted subcutaneously. Mice treated with i6A showed a drastic reduction in tumor volume. Our findings indicate that this isoprenoid end product might be used for antineoplastic therapy, an application emulating that of the lovastatin and/or farnesyl-transferase inhibitors |
| | |
Authors:
|
Chiara Laezza; Maria Notarnicola; Maria Gabriella Caruso; Caterina Messa; Marco Macchia; Simone Bertini; Filippo Minutolo; Giuseppe Portella; Laura Fiorentino; Stefania Stingo; Maurizio Bifulco |
Related Documents
:
|
11259288 - Traction force microscopy of migrating normal and h-ras transformed 3t3 fibroblasts. 8993838 - Retinoic acid and ifn inhibition of cell proliferation is associated with apoptosis in ... 12655438 - Growth suppression of a tumorigenic rat liver cell line by the anticancer agent, et-18-... 7733348 - Identification and antisense inhibition of a renin-angiotensin system in transgenic car... 6301448 - Messenger rna populations and their nuclear precursors in cultured human glioma and fet... 20501808 - Distinct roles of cytochrome p450 reductase in mitomycin c redox cycling and cytotoxicity. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 20 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2006 Mar |
Date Detail:
|
Created Date: 2006-03-01 Completed Date: 2006-04-21 Revised Date: 2012-02-15 |
Medline Journal Info:
|
Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
|
Languages: eng Pagination: 412-8 Citation Subset: IM |
Affiliation:
|
Istituto di Endocrinologia e Oncologia Sperimentale. I.E.O.S., CNR, Bari, Italy. chilaez@hotmail.com |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antineoplastic Agents / pharmacology* Cell Division / drug effects Cell Line / drug effects Cell Line, Transformed / drug effects Drug Screening Assays, Antitumor Geranyltranstransferase / antagonists & inhibitors* Isopentenyladenosine / pharmacology* Lovastatin / pharmacology Male Mevalonic Acid / metabolism Mice Neoplasm Proteins / antagonists & inhibitors* Protein Prenylation / drug effects Protein Processing, Post-Translational / drug effects* Rats Thyroid Gland / cytology |
| Chemical | |
Reg. No./Substance:
|
0/Antineoplastic Agents; 0/Neoplasm Proteins; 150-97-0/Mevalonic Acid; 75330-75-5/Lovastatin; 7724-76-7/Isopentenyladenosine; EC 2.5.1.10/Geranyltranstransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Causes of errors in polyp detection at air-contrast barium enema examination.
Next Document: Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker fo...