Resistance of acute myeloid leukemic cells to the triterpenoid CDDO-Imidazolide is associated with low caspase-8 and FADD levels

Roberta Riccioni, Mara Senese, Daniela Diverio, Viviana Riti, Gualtiero Mariani, Alessandra Boe, Francesco LoCoco, Robin Foà, Cesare Peschle, Michael Sporn, Ugo Testa

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The synthetic triterpenoid CDDO-Im-induced apoptosis of patient-derived AML blasts: 11/25 AMLs were highly sensitive, while the remaining were moderately sensitive to CDDO-Im. The addition of TRAIL significantly potentiated the cytotoxic effect of CDDO-Im, through mechanisms involving the induction of TRAIL-R1/TRAIL-R2 and downmodulation of TRAIL-R3/TRAIL-R4. Biochemical studies showed that CDDO-Im: induced a rapid and marked GSH depletion and antioxidants (GSH or NAC) completely inhibited its pro-apoptotic effect; sequentially activated caspase-8, -9 and -3; caspase inhibitors partially protected AML blasts from CDDO-Im-induced apoptosis; resistance of AML blasts to CDDO-Im-induced apoptosis correlated with low caspase-8/FADD and high Bcl-X L expression in leukemic blasts.

Original languageEnglish
Pages (from-to)1244-1258
Number of pages15
JournalLeukemia Research
Volume32
Issue number8
DOIs
Publication statusPublished - Aug 2008

Fingerprint

Caspase 8
Myeloid Cells
Apoptosis
Caspase Inhibitors
Caspase 9
Antioxidants
1-(2-cyano-3,12-dioxooleana-1,9-dien-28-oyl) imidazole

Keywords

  • Acute leukemia
  • Apoptosis
  • Drug sensitivity
  • Leukemic stem cells

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Resistance of acute myeloid leukemic cells to the triterpenoid CDDO-Imidazolide is associated with low caspase-8 and FADD levels. / Riccioni, Roberta; Senese, Mara; Diverio, Daniela; Riti, Viviana; Mariani, Gualtiero; Boe, Alessandra; LoCoco, Francesco; Foà, Robin; Peschle, Cesare; Sporn, Michael; Testa, Ugo.

In: Leukemia Research, Vol. 32, No. 8, 08.2008, p. 1244-1258.

Research output: Contribution to journalArticle

Riccioni, R, Senese, M, Diverio, D, Riti, V, Mariani, G, Boe, A, LoCoco, F, Foà, R, Peschle, C, Sporn, M & Testa, U 2008, 'Resistance of acute myeloid leukemic cells to the triterpenoid CDDO-Imidazolide is associated with low caspase-8 and FADD levels', Leukemia Research, vol. 32, no. 8, pp. 1244-1258. https://doi.org/10.1016/j.leukres.2007.12.008
Riccioni, Roberta ; Senese, Mara ; Diverio, Daniela ; Riti, Viviana ; Mariani, Gualtiero ; Boe, Alessandra ; LoCoco, Francesco ; Foà, Robin ; Peschle, Cesare ; Sporn, Michael ; Testa, Ugo. / Resistance of acute myeloid leukemic cells to the triterpenoid CDDO-Imidazolide is associated with low caspase-8 and FADD levels. In: Leukemia Research. 2008 ; Vol. 32, No. 8. pp. 1244-1258.
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