N(6)-isopentenyladenosine (i(6)A), a member of the cytokinin family of plant hormones, has potent in vitro antitumour activity in different types of human epithelial cancer cell lines. Gene expression profile analysis of i(6)A-treated cells revealed induction of genes (e.g., PPP1R15A, DNAJB9, DDIT3, and HBP1) involved in the negative regulation of cell cycle progression and reportedly up-regulated during cell cycle arrest in stress conditions. Of 6 i(6)A analogues synthesized, only the 1 with a saturated double bond of the isopentenyl side chain had in vitro antitumour activity, although weaker than that of i(6)A, suggesting that i(6)A biological activity is highly linked to its structure. In vivo analysis of i(6)A and the active analogue revealed no significant inhibition of cancer cell growth in mice by either reagent. Thus, although i(6)A may inhibit cell proliferation by regulating the cell cycle, further studies are needed to identify active analogues potentially useful in vivo.

Pharmacogenomics and analogues of the antitumor agent N6-isopentenyladenosine / F. Colombo, F.S. Falvella, L. De Cecco, M. Tortoreto, G. Pratesi, P. Ciuffreda, R. Ottria, E. Santaniello, L. Cicatiello, A. Weisz, T.A. Dragani. - In: INTERNATIONAL JOURNAL OF CANCER. - ISSN 0020-7136. - 124:9(2009 May), pp. 2179-2185.

Pharmacogenomics and analogues of the antitumor agent N6-isopentenyladenosine

P. Ciuffreda;R. Ottria;E. Santaniello;
2009

Abstract

N(6)-isopentenyladenosine (i(6)A), a member of the cytokinin family of plant hormones, has potent in vitro antitumour activity in different types of human epithelial cancer cell lines. Gene expression profile analysis of i(6)A-treated cells revealed induction of genes (e.g., PPP1R15A, DNAJB9, DDIT3, and HBP1) involved in the negative regulation of cell cycle progression and reportedly up-regulated during cell cycle arrest in stress conditions. Of 6 i(6)A analogues synthesized, only the 1 with a saturated double bond of the isopentenyl side chain had in vitro antitumour activity, although weaker than that of i(6)A, suggesting that i(6)A biological activity is highly linked to its structure. In vivo analysis of i(6)A and the active analogue revealed no significant inhibition of cancer cell growth in mice by either reagent. Thus, although i(6)A may inhibit cell proliferation by regulating the cell cycle, further studies are needed to identify active analogues potentially useful in vivo.
Antitumoural; Isopentenyl transferase; Microarray; TRIT1; Tumour suppressor
Settore BIO/10 - Biochimica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/64546
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