{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T23:36:39Z","timestamp":1775950599266,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,3,1]],"date-time":"2006-03-01T00:00:00Z","timestamp":1141171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2006,3]]},"abstract":"<jats:p>\n                    The physiological effects of a variety of N6\u2010substituted 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\u2010proliferative effect of N6\u2010isopentenyladenosine (i\n                    <jats:sup>6<\/jats:sup>\n                    A), an adenosine and isoprenoid derivative, in a thyroid cell system, FRTL\u20105 wild\u2010type, and K\u2010\n                    <jats:italic>ras<\/jats:italic>\n                    transformed KiMol cells. Addition of i\n                    <jats:sup>6<\/jats:sup>\n                    A to FRTL\u20105 cells caused a dose\u2010dependent arrest of the G\n                    <jats:sub>0<\/jats:sub>\n                    \u2010G\n                    <jats:sub>1<\/jats:sub>\n                    cell phase transition associated with a reduction of cells in the S phase that was much more evident in KiMol cells. I\n                    <jats:sup>6<\/jats:sup>\n                    A arrested tumor cell proliferation by inhibiting farnesyl diphosphate synthase (FPPS) and protein prenylation. Indeed the addition of farnesol reversed these effects and i\n                    <jats:sup>6<\/jats:sup>\n                    A affected protein prenylation, in particular lamin B processing. I\n                    <jats:sup>6<\/jats:sup>\n                    A 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. I\n                    <jats:sup>6<\/jats:sup>\n                    A inhibited FPPS activity more efficaciously in KiMol cells than in normal FRTL\u20105. Moreover, the i\n                    <jats:sup>6<\/jats:sup>\n                    A anti\u2010proliferative effect was evaluated in vivo in a nude mouse xenograft model, where KiMol cells were implanted subcutaneously. Mice treated with i\n                    <jats:sup>6<\/jats:sup>\n                    A 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 farnesyltransferase inhibitors.\u2014Laezza, C., Notarnicola, M., Caruso, M. G., Messa, C., Macchia, M., Bertini, S., Minutolo, F., Portella, G., Fiorentino, L., Stingo, S., Bifulco, M. N6\u2010isopentenyladenosine arrests tumor cell proliferation by inhibiting farnesyl diphosphate synthase and protein prenylation.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    20, 412\u2013418 (2006)\n                  <\/jats:p>","DOI":"10.1096\/fj.05-4044lsf","type":"journal-article","created":{"date-parts":[[2006,2,28]],"date-time":"2006-02-28T15:42:59Z","timestamp":1141141379000},"page":"412-418","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["N6\u2010isopentenyladenosine arrests tumor cell proliferation by inhibiting farnesyl diphosphate synthase and protein prenylation"],"prefix":"10.1096","volume":"20","author":[{"given":"Chiara","family":"Laezza","sequence":"first","affiliation":[{"name":"Istituto di Endocrinologia e Oncologia Sperimentale. I.E.O.S., CNR  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Notarnicola","sequence":"additional","affiliation":[{"name":"Laboratorio di Biochimica; I.R.C.C.S. \u201cS. de Bellis\u201d Castellana G. (Bari)  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Gabriella","family":"Caruso","sequence":"additional","affiliation":[{"name":"Laboratorio di Biochimica; I.R.C.C.S. \u201cS. de Bellis\u201d Castellana G. (Bari)  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Messa","sequence":"additional","affiliation":[{"name":"Laboratorio di Biochimica; I.R.C.C.S. \u201cS. de Bellis\u201d Castellana G. (Bari)  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Macchia","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche Universit\u00e0di Pisa  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Bertini","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche Universit\u00e0di Pisa  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippo","family":"Minutolo","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche Universit\u00e0di Pisa  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Portella","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia e Patologia Cellulare e Molecolare \u201cL.Califano,\u201d Universit\u00e0 di Napoli \u201cFederico II,\u201d  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche Universit\u00e0 di Salerno  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Stingo","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche Universit\u00e0 di Salerno  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Bifulco","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmaceutiche Universit\u00e0 di Salerno  Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1997.3610"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6603(08)60375-X"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.4.1113"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"9961","DOI":"10.1016\/S0021-9258(18)92913-3","article-title":"Evidence for isopentenyladenosine modification on a cell cycle\u2010regulated protein","volume":"266","author":"Faust J. 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