Ribavirin as a tri-targeted antitumor repositioned drug

Oncology Reports
Erick De la Cruz-HernandezAlfonso Dueñas-Gonzalez

Abstract

The aim of the present study was to demonstrate that ribavirin, a known inhibitor of eIF4E and inosine 5'-phosphate dehydrogenase (IMPDH), also inhibits histone methyltransferase zeste homolog 2 (EZH2). A computational searching revealed that ribavirin has a high structural similarity to 3-deazaneplanocin A (DZNep). The growth inhibitory effects of ribavirin as well as its effects upon epigenetic enzymes were evaluated in various cancer cell lines. siRNA assays were used to downregulate eIF4E, EZH2 and IMPDH to determine the contribution of these targets to the growth inhibitory effects of ribavirin. Ribavirin decreased EZH2 expression, inhibited histone methyltransferase activity and decreased H3K27 trimethylation. Ribavirin induced variable growth inhibition in a number of cell lines and downregulation of the targets, EZH2, eIF4E and IMPDH1 and 2 by siRNA led to comparable growth inhibition while no significant further reduction in viability was observed when siRNA transfected cells were treated with ribavirin. The results showed that ribavirin inhibits these cancer targets and should thus be studied for cancer therapy.

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Citations

Nov 1, 2017·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·J CaoD Chen
Mar 1, 2018·Oncotarget·Joshua CasaosNicolas Skuli
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May 6, 2020·Pharmaceutics·Filipa Moreira-SilvaCarmen Jerónimo
Sep 28, 2020·FEBS Open Bio·Vicente Morales-GarciaErick de la Cruz-Hernandez
Nov 17, 2020·Genome Génome / Conseil National De Recherches Canada·Wenxia LuoTed M Lakowski
Jul 3, 2019·Molecular Cancer Therapeutics·Joshua CasaosNicolas Skuli
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Dec 15, 2020·Frontiers in Oncology·Michel Montalvo-CasimiroLuis A Herrera
Feb 17, 2021·Journal of Medicinal Chemistry·Angela Fan, Phillip P Sharp

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