N6-isopentenyladenosine inhibits cell proliferation and induces apoptosis in a human colon cancer cell line DLD1.
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.
Laezza
Chiara
C
Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Naples, Italy. chilaez@hotmail.com
Caruso
Maria Gabriella
MG
Gentile
Teresa
T
Notarnicola
Maria
M
Malfitano
Anna Maria
AM
Di Matola
Tiziana
T
Messa
Caterina
C
Gazzerro
Patrizia
P
Bifulco
Maurizio
M
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007541:Isopentenyladenosine / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D007541:Isopentenyladenosine; D048031:JNK Mitogen-Activated Protein Kinases