Clinically tolerable concentrations of arsenic trioxide induce p53-independent cell death and repress NF-kappa B activation in Ewing sarcoma cells

International Journal of Cancer. Journal International Du Cancer
Julie Mathieu, Françoise Besançon

Abstract

Ewing sarcoma (ES), a highly malignant pediatric tumor, is consistently associated with translocations that fuse the EWS gene with a member of the ETS family gene, most commonly FLI-1. Despite significant advances with multiagent chemotherapy, surgery and radiotherapy, about 40% of ES patients still die from the disease. It is therefore necessary to explore novel agents for possible treatment of this tumor. Here the authors investigated the sensitivity of ES cells to clinically tolerable concentrations of arsenic trioxide (As2O3), a compound known to induce differentiation and apoptosis of other types of malignant cells. The authors report that As2O3 uniformly induced death of 6 ES-derived cell lines irrespective of their p53 status. As2O3 resulted in an apoptotic phenotype which was inhibited by the broad-spectrum caspase inhibitor ZVAD-fmk. These effects correlated with prolonged c-jun N-terminal kinase activation, which is a signal for apoptosis in ES cells. As2O3 also decreased basal and cytokine-induced NF-kappa B activity. Since the authors previously demonstrated that NF-kappa B exerts an antiapoptotic action in ES cells, As2O3 treatment may also result in a sensitization of these cells to other drugs used in combination...Continue Reading

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Citations

Dec 25, 2010·The Journal of Clinical Investigation·Elspeth M BeauchampAykut Uren
Sep 10, 2013·Surgical Oncology Clinics of North America·Derek J Erstad, James C Cusack
Jun 26, 2007·British Journal of Haematology·Richard A CampbellJames R Berenson
Apr 24, 2015·Frontiers in Oncology·Santiago Rello-VaronaOscar Martínez Tirado
Dec 1, 2009·Melanoma Research·Valerie TrappJohn P Fruehauf
Jul 28, 2020·Pharmaceuticals·Angel Escamilla-RamírezCristina Trejo-Solís
Oct 26, 2016·International Journal of Oncology·Karen A BoehmeFrank Traub
Feb 27, 2021·Pediatric Hematology and Oncology·Michael AbeleMartin Ebinger
Nov 1, 2007·Chemical Research in Toxicology·Konstantin Salnikow, Anatoly Zhitkovich

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