Laezza Chiara, Caruso Maria Gabriella, Gentile Teresa, Notarnicola Maria, Malfitano Anna Maria, Di Matola Tiziana, Messa Caterina, Gazzerro Patrizia, Bifulco Maurizio
Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Naples, Italy.
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.
N⁶ -异戊烯基腺苷（i6A）是一种修饰核苷，其异戊烯基有五个原子，源自甲羟戊酸，可在多种肿瘤细胞系中诱导肿瘤细胞增殖抑制和凋亡。在本研究中，我们报道N⁶ -异戊烯基腺苷抑制DLD1人结肠癌细胞的增殖并促进其凋亡。它通过抑制DNA合成来抑制细胞增殖，导致细胞周期停滞，这与细胞周期蛋白E、细胞周期蛋白A和细胞周期蛋白D1水平的降低以及细胞周期蛋白依赖性激酶抑制剂p21waf和p27kip1水平的相应升高相关。此外，它通过膜联蛋白V阳性细胞数量增加、抗凋亡产物下调和半胱天冬酶-3激活来诱导凋亡。N⁶ -异戊烯基腺苷的凋亡作用伴随着c-jun氨基末端激酶（JNK）的持续磷酸化和激活，进而诱导c-jun磷酸化。总体而言，我们的数据表明JNK可能在i6A介导的DLD1人结肠癌细胞凋亡中发挥重要作用。
