Tris (dibenzylideneacetone) dipalladium: a small-molecule palladium complex is effective in inducing apoptosis in chronic lymphocytic leukemia B-cells

Neil E. Kay, Traci Sassoon, Charla Secreto, Sutapa Sinha, Tait D. Shanafelt, Asish K. Ghosh, Jack L. Arbiser

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Here we tested impact of Tris (dibenzylideneacetone) dipalladium (Tris-DBA) on chronic lymphocytic leukemia (CLL) B-cell survival. Indeed, treatment of CLL B-cells with Tris-DBA induced apoptosis in a dose-dependent manner irrespective of IgVH mutational status. Further analyses suggest that Tris-DBA-induced apoptosis involves reduced expression of the anti-apoptotic proteins Bcl-xL, and XIAP with an upregulation of the pro-apoptotic protein BIM in CLL B-cells. Our findings also indicate that Tris-DBA targets the ribosomal protein (rp)-S6, an essential component of the Akt/mTOR signaling axis in CLL B-cells. Of interest, CLL bone marrow stromal cells were unable to protect the leukemic B cells from Tris-DBA-induced apoptosis in an in vitro co-culture system. Finally, co-administration of Tris-DBA and the purine nucleoside analog fludarabine (F-ara-A) augmented CLL B-cell apoptosis levels in vitro showing synergistic effects. In total, Tris-DBA is effective at inducing apoptosis in CLL B-cells even in the presence of stromal cells likely by targeting directly the signal mediator, rpS6.

Original languageEnglish (US)
Pages (from-to)2409-2416
Number of pages8
JournalLeukemia and Lymphoma
Volume57
Issue number10
DOIs
StatePublished - Oct 2 2016

Keywords

  • CLL
  • Tris-DBA
  • fludarabine

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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