N6‐isopentenyladenosine inhibits cell proliferation and induces apoptosis in a human colon cancer cell line DLD1 |
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Authors: | Chiara Laezza Maria Gabriella Caruso Teresa Gentile Maria Notarnicola Anna Maria Malfitano Tiziana Di Matola Caterina Messa Patrizia Gazzerro Maurizio Bifulco |
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Institution: | 1. Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Naples, Italy;2. National Institute of Digestive Diseases, “S. de Bellis” Castellana Grotte, (BA), Italy;3. Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli “Federico II,” via Pansini 80131 Naples, Italy;4. Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Via Ponte don Melillo, 84084 Fisciano Salerno, Italy |
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Abstract: | N6‐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 N6‐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 N6‐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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Keywords: | N6‐isopentenyladenosine apoptosis JNK colon cancer |
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