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N6-isopentenyladenosine inhibits cell proliferation and induces apoptosis in a human colon cancer cell line DLD1

✍ Scribed by Chiara Laezza; Maria Gabriella Caruso; Teresa Gentile; Maria Notarnicola; Anna Maria Malfitano; Tiziana Di Matola; Caterina Messa; Patrizia Gazzerro; Maurizio Bifulco

Publisher
John Wiley and Sons
Year
2009
Tongue
French
Weight
326 KB
Volume
124
Category
Article
ISSN
0020-7136

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✦ Synopsis

Abstract

N^6^‐isopentenyladenosine (i6A) is a modified nucleoside with a pentaatomic isopentenyl derived from mevalonate that induces inhibition of tumor cell proliferation and apoptosis in several tumor cell lines. In this study, we reported that N^6^‐isopentenyladenosine inhibited the proliferation and promotes apoptosis in DLD1 human colon cancer cells. It suppressed the proliferation of cells through inhibition of DNA synthesis, causing a cell cycle arrest that correlated with a decrease in the levels of cyclin E, cyclin A and cyclin D1 and with a concomitant increase in the levels of cyclin‐dependent kinase inhibitor p21waf and p27kip1. Moreover, it induced apoptosis through an increase in the number of annexin V‐positive cells, a downregulation of antiapoptotic products and caspase‐3 activation. The apoptotic effects of N^6^‐isopentenyladenosine were accompanied by sustained phosphorylation and activation of c‐jun N‐terminal kinase (JNK) that induced phosphorylation of c‐jun. Overall, our data show that JNK, could play an important role in i6A‐mediated apoptosis in DLD1 human colon cancer cells © 2008 Wiley‐Liss, Inc.

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