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Pharmacogenomics and analogues of the antitumour agent N 6 ‐isopentenyladenosine
Author(s) -
Colombo Francesca,
Falvella F. Stefania,
De Cecco Loris,
Tortoreto Monica,
Pratesi Graziella,
Ciuffreda Pierangela,
Ottria Roberta,
Santaniello Enzo,
Cicatiello Luigi,
Weisz Alessandro,
Dragani Tommaso A.
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24168
Subject(s) - cell cycle , in vivo , cell growth , cell culture , in vitro , cell cycle checkpoint , biology , cell , cytokinin , g1 phase , gene , biological activity , biochemistry , chemistry , auxin , genetics
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 . © 2008 Wiley‐Liss, Inc.