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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.

Riccioni, R., Senese, M., Diverio, D., Riti, V., Mariani, G., Boe, A., et al. (2008). Resistance of acute myeloid leukemic cells to the triterpenoid CDDO-Imidazolide is associated with low caspase-8 and FADD levels. LEUKEMIA RESEARCH, 32(8), 1244-1258 [10.1016/j.leukres.2007.12.008].

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

LO COCO, FRANCESCO;
2008-01-01

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.
2008
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/15 - MALATTIE DEL SANGUE
English
Con Impact Factor ISI
acute leukemia; apoptosis; drug sensitivity; leukemic stem cells; 2 cyano 3,12 dioxooleana 1,9 dien 28 oic acid imidazolide; caspase 3; caspase 9; death receptor 4; death receptor 5; Fas associated death domain protein; glutathione; triterpenoid; tumor necrosis factor related apoptosis inducing ligand receptor 3; acute granulocytic leukemia; apoptosis; article; cancer resistance; clinical article; controlled study; cytotoxicity; drug effect; drug sensitivity; enzyme activation; enzyme activity; flow cytometry; human cell; immunophenotyping; leukemia cell; mitochondrial membrane potential; priority journal; protein expression; apoptosis; Caspase 8; neoplasm; enzyme activation; fas-associated death domain protein; humans; imidazoles; leukemia, myeloid, acute; oleanolic acid; TNF-related apoptosis-inducing ligand; tumor cells, cultured
Riccioni, R., Senese, M., Diverio, D., Riti, V., Mariani, G., Boe, A., et al. (2008). Resistance of acute myeloid leukemic cells to the triterpenoid CDDO-Imidazolide is associated with low caspase-8 and FADD levels. LEUKEMIA RESEARCH, 32(8), 1244-1258 [10.1016/j.leukres.2007.12.008].
Riccioni, R; Senese, M; Diverio, D; Riti, V; Mariani, G; Boe, A; LO COCO, F; Foa, R; Peschle, C; Sporn, M; Testa, U
Articolo su rivista
01 - Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/8102
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