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

Sampath Ramachandiran, Joan Cain, Albert Liao, Yanjuan He, Xiangxue Guo, Lawrence H. Boise, Haian Fu, Lee Ratner, Hanna Jean Khoury, Leon Bernal-Mizrachi

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish
Pages (from-to)784-790
Number of pages7
JournalLeukemia Research
Volume36
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • EBV
  • HHV-8
  • HTLV-1
  • Lymphomas
  • Smac mimetics
  • XIAP

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