Enhanced autophagy follows LMP1 expression disruption in EBV+ P3HR1 cells treated with arsenic trioxide.

Abstract

Event Abstract Back to Event Enhanced autophagy follows LMP1 expression disruption in EBV+ P3HR1 cells treated with arsenic trioxide. Abderezak Zebboudj1*, Chafia Touil-Boukoffa1 and Mehdi Bourouba1 1 University of Sciences and Technologies Houari Boumediene (USTHB), FSB, Algeria Introduction : The Epstein Barr Virus (EBV) latency is associated with several malignancies among which nasopharyngeal carcinoma (NPC) and immunocompromised patients lymphoma. Expression and signaling of the major viral oncogene latent membrane protein 1 (LMP1) is essential to the immortalization of NPC cells and in vitro of B lymphocytes. Arsenic trioxide (ATO) treatment was reported to induce apoptosis in NPC cells via LMP1 down-regulation. Conversely, autophagy has been linked to LMP1 expression in B cells and survival. Here, we analyzed the anti-proliferative activity of ATO on P3HR1 EBV+ lymphoblastoid cells and assessed it's effect on apoptosis, autophagy and LMP1 expression. Materials and Methods : LMP1 expressing cells P3HR1 were treated with different concentrations of ATO. Apoptosis was measured by annexin V/PI double staining. DiOC6 labeling was assessed for mitochondrial potential (ΔΨm). Degree of autophagy was assessed based on LC3BI/LC3BII conversion. The anti-proliferative effect of ATO was studied using soft agar clonogenicity test. LMP1 expression and transcription was analyzed by western blot and Q-RT-PCR. Results : Our results show that ATO treatment leads to increased annexin V labeling and loss of mitochondrial potential in P3HR1 cells. We found that apoptosis is accompanied with enhanced autophagic activity as indicated by LC3B profile. Our results also indicate that ATO treatment induces disruption of LMP1 expression after 72H of treatment and inhibition of its transcription. Thus effects were associated with suppression of cells clonogenicity. Conclusion : Our study suggests that ATO cytotoxicity in P3HR1 cells occurs via induction of apoptosis and up-regulation of autophagic activity. These processes may occur as a consequence of LMP1 transcription repression and depletion of cellular LMP1 pools. Taken together, our data suggest that ATO may regulate negatively tumor cells survival by suppressing LMP1 anti-apoptotic signaling and enhancing autophagic cell death. Acknowledgements This work was performed and co-directed in collaboration with Dr Mounira Chelbi- Alix and Dr Sébastien Nisole team "INSERM UMR-S 1124, Université Paris Descartes,Paris, France". We thank Pr Mohamed Seghier "Institut Pasteur d'Algérie" for material and technical support. Keywords: ATO, apoptosis and autophagy, LMP1, ebv, Lymphoma, B-Cell Conference: The First International Congress of Immunology and Molecular Immunopathology (CIMIP2014), Tlemcen, Algeria, 17 Oct - 20 Oct, 2014. Presentation Type: Oral Poster Presentation Topic: Lymphoproliferative disorders Citation: Zebboudj A, Touil-Boukoffa C and Bourouba M (2014). Enhanced autophagy follows LMP1 expression disruption in EBV+ P3HR1 cells treated with arsenic trioxide.. Front. Immunol. Conference Abstract: The First International Congress of Immunology and Molecular Immunopathology (CIMIP2014). doi: 10.3389/conf.fimmu.2014.04.00007 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 10 Sep 2014; Published Online: 01 Dec 2014. * Correspondence: Mr. Abderezak Zebboudj, University of Sciences and Technologies Houari Boumediene (USTHB), FSB, Bab-Ezzouar, Algiers, 16111, Algeria, azebboudj@usthb.dz Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Abderezak Zebboudj Chafia Touil-Boukoffa Mehdi Bourouba Google Abderezak Zebboudj Chafia Touil-Boukoffa Mehdi Bourouba Google Scholar Abderezak Zebboudj Chafia Touil-Boukoffa Mehdi Bourouba PubMed Abderezak Zebboudj Chafia Touil-Boukoffa Mehdi Bourouba Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.