Di Matola, Tiziana (2006) N6-isopentenyladenosine arrests tumor cell proliferation by inhibiting farnesyl diphosphate synthase and protein prenylation. [Tesi di dottorato] (Inedito)

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Tipologia del documento:	Tesi di dottorato
Lingua:	English
Titolo:	N6-isopentenyladenosine arrests tumor cell proliferation by inhibiting farnesyl diphosphate synthase and protein prenylation
Autori:	Autore Email Di Matola, Tiziana [non definito]
Data:	2006
Tipo di data:	Pubblicazione
Numero di pagine:	52
Istituzione:	Università degli Studi di Napoli Federico II
Dipartimento:	Biologia e patologia cellullare e molecolare "L. Califano"
Dottorato:	Oncologia ed endocrinologia molecolare
Ciclo di dottorato:	17
Coordinatore del Corso di dottorato:	nome email Vecchio, Giancarlo [non definito]
Tutor:	nome email Rossi, Guido [non definito]
Data:	2006
Numero di pagine:	52
Parole chiave:	Inibitori farnesil trasferasi; Cellule tiroidee tumorali; Terapia anticancro
Settori scientifico-disciplinari del MIUR:	Area 06 - Scienze mediche > MED/04 - Patologia generale
Depositato il:	02 Set 2008
Ultima modifica:	30 Apr 2014 19:34
URI:	http://www.fedoa.unina.it/id/eprint/2894

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 I 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 it 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 cells. 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

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