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

Int J Cancer. 2009 Mar 15;124(6):1322-9. doi: 10.1002/ijc.24056.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Cycle / drug effects
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • Colonic Neoplasms / pathology*
  • DNA Fragmentation / drug effects
  • Enzyme Activation / drug effects
  • Flow Cytometry
  • Humans
  • Isopentenyladenosine / pharmacology*
  • JNK Mitogen-Activated Protein Kinases / drug effects
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics


  • RNA, Messenger
  • RNA, Neoplasm
  • Isopentenyladenosine
  • JNK Mitogen-Activated Protein Kinases