N6-isopentenyladenosine arrests tumor cell proliferation by inhibiting farnesyl diphosphate synthase and protein prenylation

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Chiara LaezzaMaurizio Bifulco

Abstract

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 subcut...Continue Reading

References

Jul 1, 1976·Proceedings of the Royal Society of Medicine·R W Hoile
Aug 8, 1975·Annals of the New York Academy of Sciences·A MittelmanG B Chheda
Apr 1, 1992·Journal of Neurochemistry·I van der PloegB B Fredholm
Feb 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·H M Laten, S Zahareas-Doktor
Jun 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·F S Ambesi-ImpiombatoH G Coon
Nov 15, 1981·International Journal of Cancer. Journal International Du Cancer·A FuscoN Tsuchida
Jan 1, 1984·Progress in Nucleic Acid Research and Molecular Biology·H Kersten
Jan 1, 1995·Annual Review of Pharmacology and Toxicology·M E Olah, G L Stiles
Jan 1, 1996·Annual Review of Biochemistry·F L Zhang, P J Casey
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·C LaezzaM Bifulco
Apr 13, 2000·Biochimica Et Biophysica Acta·M Sinensky
Dec 26, 2001·Cytokine & Growth Factor Reviews·Richard Kinh Gian Do, Selina Chen-Kiang
Sep 6, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Giuseppe PortellaMaurizio Bifulco
Nov 9, 2004·Cancer Treatment Reviews·Matthijs R GraafHenk-Jan Guchelaar

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Citations

Jan 22, 2011·Chemical Reviews·Lan Lin, Ren Xiang Tan
Oct 19, 2011·Nucleic Acid Therapeutics·Mehdi RajabiEnzo Santaniello
Sep 4, 2014·Journal of Medicinal Chemistry·Mario ScrimaAnna Maria D'Ursi
Jun 18, 2010·Phytochemistry·Jirí VollerMiroslav Strnad
Dec 6, 2008·International Journal of Cancer. Journal International Du Cancer·Chiara LaezzaMaurizio Bifulco
Jan 7, 2009·International Journal of Cancer. Journal International Du Cancer·Francesca ColomboTommaso A Dragani
Jul 27, 2014·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Elena CiagliaMaurizio Bifulco
Apr 3, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Li WangGuang-Qin Guo
Apr 2, 2014·Redox Biology·Alice DassanoFrancesca Colombo
Jan 16, 2007·Biochimica Et Biophysica Acta·Jack WoodsMark A Smith
Nov 5, 2016·International Journal of Cancer. Journal International Du Cancer·Elena CiagliaMaurizio Bifulco
Mar 28, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Miao LiLijun Zhou
Sep 9, 2017·International Journal of Cancer. Journal International Du Cancer·Elena CiagliaMaurizio Bifulco
Jun 13, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mark SeegobinR J Neil Emery
Nov 23, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Simona PisantiMaurizio Bifulco
Mar 10, 2011·Magnetic Resonance in Chemistry : MRC·Silvana CasatiPierangela Ciuffreda
Feb 17, 2007·International Journal of Cancer. Journal International Du Cancer·Monica SpinolaTommaso A Dragani
Jun 30, 2012·Angewandte Chemie·Thomas CarellMirko Wagner
Dec 13, 2017·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Antonietta SantoroMaurizio Bifulco
Oct 4, 2019·Journal of Cellular Physiology·Milad AshrafizadehSaeed Samarghandian
Dec 23, 2019·RSC Medicinal Chemistry·Pimyupa ManaswiyoungkulPatrick T Gunning

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