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

Fiche publication

Date publication

janvier 2018

Journal

Epigenetics insights

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BRONNER Christian , Dr HAMICHE Ali

Tous les auteurs :
Razvi SS, Choudhry H, Hasan MN, Hassan MA, Moselhy SS, Abualnaja KO, Zamzami MA, Kumosani TA, Al-Malki AL, Halwani MA, Ibrahim A, Hamiche A, Bronner C, Asami T, Alhosin M

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/30515476

Résumé

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.