The SMAC mimetic RMT5265.2HCL induces apoptosis in EBV AND HTLV-I associated lymphoma cells by inhibiting XIAP and promoting the mitochondrial release of cytochrome C and Smac

• Type of Material: Article
• Authors: Sampath Ramachandiran, Emory University; Joan Cain, Emory University; Albert Liao, Emory University; Yanjuan He, Emory University; Xiangxue Guo, Emory University; Lawrence Boise, Emory University; Haian Fu, Emory University; Lee Ratner, Washington University; H Jean Khoury, Emory University; Leon Bernal-Mizrachi, Emory University
• Language: English
• Date: 2012-06
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.leukres.2011.12.024
• Title of Journal or Parent Work: Leukemia Research
• ISSN: 0145-2126
• Volume: 36
• Issue: 6
• Start Page: 784
• End Page: 790
• Grant/Funding Information: L.H.B received funding support from the NIH (CA127910 and CA129968) and a GCCDSW, L.R. was supported by the National Institute of Health (NIH, CA94056, CA10073 and CA63417) and L.B-M received funding from the Crissey Hematology and Medical Oncology Research Fund.
• Keywords: HTLV-1; HHV-8; Smac mimetics; XIAP; EBV; lymphomas
• Research Categories: Health Sciences, Oncology

Abstract

The inhibitors of apoptosis (IAP) are important regulators of apoptosis. However, little is known about the capacity of Smac mimetics (IAP inhibitor) to overcome virally-associated-lymphoma’s (VAL) resistance to apoptosis. Here, we explored the pro-apoptotic effect of a novel Smac mimetic, RMT5265.2HCL (RMT) in VAL cells. RMT improved the sensitivity to apoptosis in EBV- and to some extend in HTLV-1- but not in HHV-8-VAL. Furthermore, we identified that RMT promotes caspase 3 and 9 cleavage by inhibiting XIAP and inducing the mitochondrial efflux of Smac and cytochrome C. This investigation further support exploring the use of Smac inhibitors in VAL.