Pharmacogenomics and analogues of the antitumour agent N 6-isopentenyladenosine

Francesca Colombo, F. Stefania Falvella, Loris De Cecco, Monica Tortoreto, Graziella Pratesi, Pierangela Ciuffreda, Roberta Ottria, Enzo Santaniello, Luigi Cicatiello, Alessandro Weisz, Tommaso A. Dragani

Research output: Contribution to journalArticlepeer-review

Abstract

N6-isopentenyladenosine (i6A), 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 i6A-treated cells revealed induction of genes (e.g., PPP1R15A, DNAJB9, DDIT3, and HBP1) involved in the negative regulation of cell cycle progression and reportedly upregulated during cell cycle arrest in stress conditions. Of 6 i6A 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 i6A, suggesting that i 6A biological activity is highly linked to its structure. In vivo analysis of i6A and the active analogue revealed no significant inhibition of cancer cell growth in mice by either reagent. Thus, although i6A may inhibit cell proliferation by regulating the cell cycle, further studies are needed to identify active analogues potentially useful in vivo.

Original languageEnglish
Pages (from-to)2179-2185
Number of pages7
JournalInternational Journal of Cancer
Volume124
Issue number9
DOIs
Publication statusPublished - May 1 2009

Keywords

  • Antitumoural
  • Isopentenyl transferase
  • Microarray
  • TRIT1
  • Tumour suppressor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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