Identification of Deregulated Signaling Pathways in Jurkat Cells in Response to a Novel Acylspermidine Analogue-N 4 -Erucoyl Spermidine

Natural polyamines such as putrescine, spermidine, and spermine are crucial in the cell proliferation and maintenance in all the eukaryotes. However, the requirement of polyamines in tumor cells is stepped up to maintain tumorigenicity. Many synthetic polyamine analogues have been designed recently...

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Veröffentlicht in:Epigenetics insights 2018, Vol.11, p.2516865718814543
Hauptverfasser: Razvi, Syed Shoeb, Choudhry, Hani, Hasan, Mohammed Nihal, Hassan, Mohammed A, Moselhy, Said Salama, Abualnaja, Khalid Omer, Zamzami, Mazin A, Kumosani, Taha Abduallah, Al-Malki, Abdulrahman Labeed, Halwani, Majed A, Ibrahim, Abdulkhaleg, Hamiche, Ali, Bronner, Christian, Asami, Tadao, Alhosin, Mahmoud
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Sprache:eng
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Zusammenfassung:Natural polyamines such as putrescine, spermidine, and spermine are crucial in the cell proliferation and maintenance in all the eukaryotes. However, the requirement of polyamines in tumor cells is stepped up to maintain tumorigenicity. Many synthetic polyamine analogues have been designed recently to target the polyamine metabolism in tumors to induce apoptosis. N -Erucoyl spermidine (designed as N -Eru), a novel acylspermidine derivative, has been shown to exert selective inhibitory effects on both hematological and solid tumors, but its mechanisms of action are unknown. In this study, RNA sequencing was performed to investigate the anticancer mechanisms of N -Eru-treated T-cell acute lymphoblastic leukemia (ALL) cell line (Jurkat cells), and gene expression was examined through different tools. We could show that many key oncogenes including , and were downregulated, whereas several tumor suppressor genes such as were upregulated. Data obtained through RNA-Seq further showed that N -Eru inhibited the NOTCH/Wnt/JAK-STAT axis. This study also indicated that N -Eru-induced apoptosis could involve several key signaling pathways in cancer. Altogether, our results suggest that N -Eru is a promising drug to treat ALL.
ISSN:2516-8657
2516-8657
DOI:10.1177/2516865718814543