Tris (dibenzylideneacetone) dipalladium

a small-molecule palladium complex is effective in inducing apoptosis in chronic lymphocytic leukemia B-cells

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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)1-8
Number of pages8
JournalLeukemia and Lymphoma
DOIs
StateAccepted/In press - Jan 17 2016

Fingerprint

Palladium
B-Cell Chronic Lymphocytic Leukemia
Apoptosis
Apoptosis Regulatory Proteins
Ribosomal Protein S6
Purine Nucleosides
tris(dibenzylideneacetone)dipalladium
Stromal Cells
Coculture Techniques
Mesenchymal Stromal Cells
Cell Survival
B-Lymphocytes
Up-Regulation

Keywords

  • CLL
  • fludarabine
  • Tris-DBA

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Tris (dibenzylideneacetone) dipalladium : a small-molecule palladium complex is effective in inducing apoptosis in chronic lymphocytic leukemia B-cells. / Kay, Neil Elliot; Sassoon, Traci; Secreto, Charla; Sinha, Sutapa; Shanafelt, Tait D.; Ghosh, Asish K.; Arbiser, Jack L.

In: Leukemia and Lymphoma, 17.01.2016, p. 1-8.

Research output: Contribution to journalArticle

Kay, Neil Elliot ; Sassoon, Traci ; Secreto, Charla ; Sinha, Sutapa ; Shanafelt, Tait D. ; Ghosh, Asish K. ; Arbiser, Jack L. / Tris (dibenzylideneacetone) dipalladium : a small-molecule palladium complex is effective in inducing apoptosis in chronic lymphocytic leukemia B-cells. In: Leukemia and Lymphoma. 2016 ; pp. 1-8.
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