Identification of Deregulated Signaling Pathways in Jurkat Cells in Response to a Novel Acylspermidine Analogue-N4-Erucoyl Spermidine.
作者： Syed Shoeb Razvi , Hani Choudhry , Mohammed Nihal Hasan , Mohammed A Hassan , Said Salama Moselhy
关键词: Chemistry 、 Putrescine 、 Cell growth 、 Cell biology 、 Spermine 、 Spermidine 、 Wnt signaling pathway 、 Signal transduction 、 Polyamine 、 Jurkat cells
摘要: Natural polyamines such as putrescine, spermidine, and spermine are crucial in the cell proliferation maintenance all eukaryotes. However, requirement of tumor cells is stepped up to maintain tumorigenicity. Many synthetic polyamine analogues have been designed recently target metabolism tumors induce apoptosis. N4-Erucoyl spermidine (designed N4-Eru), a novel acylspermidine derivative, has shown exert selective inhibitory effects on both hematological solid tumors, but its mechanisms action unknown. In this study, RNA sequencing was performed investigate anticancer N4-Eru-treated T-cell acute lymphoblastic leukemia (ALL) line (Jurkat cells), gene expression examined through different tools. We could show that many key oncogenes including NDRG1, CACNA1G, TGFBR2, NOTCH1,2,3, UHRF1, DNMT1,3, HDAC1,3, KDM3A, KDM4B, KDM4C, FOS, SATB1 were downregulated, whereas several suppressor genes CDKN2AIPNL, KISS1, DDIT3, TP53I13, PPARG, FOXP1 upregulated. Data obtained RNA-Seq further showed N4-Eru inhibited NOTCH/Wnt/JAK-STAT axis. This study also indicated N4-Eru-induced apoptosis involve signaling pathways cancer. Altogether, our results suggest promising drug treat ALL.
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