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2017 ; 8
(20
): 32550-32565
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
High-dose ascorbate and arsenic trioxide selectively kill acute myeloid leukemia
and acute promyelocytic leukemia blasts in vitro
#MMPMID28427227
Noguera NI
; Pelosi E
; Angelini DF
; Piredda ML
; Guerrera G
; Piras E
; Battistini L
; Massai L
; Berardi A
; Catalano G
; Cicconi L
; Castelli G
; D'Angiò A
; Pasquini L
; Graziani G
; Fioritoni G
; Voso MT
; Mastrangelo D
; Testa U
; Lo-Coco F
Oncotarget
2017[May]; 8
(20
): 32550-32565
PMID28427227
show ga
The use of high-dose ascorbate (ASC) for the treatment of human cancer has been
attempted several decades ago and has been recently revived by several in vitro
and in vivo studies in solid tumors. We tested the cytotoxic effects of ASC,
alone or in combination with arsenic trioxide (ATO) in acute myeloid leukemia
(AML) and acute promyelocytic leukemia (APL). Leukemic cell lines and primary
blasts from AML and APL patients were treated with graded concentrations of ASC,
alone or in association with standard concentration (1 ?M) of ATO. The ASC/ATO
combination killed myeloid blasts, including leukemic CD34+ cells, while sparing
CD34+ progenitors obtained from normal cord blood and bone marrow. Actually,
approximately one-third (11/36) of primary AML cases were highly sensitive to the
ASC/ATO combination. The mechanism of cell killing appeared to be related to
increased oxidative stress and overproduction of ROS in a non-quantitative
fashion, which resulted in induction of apoptosis. These effects were reverted by
the addition of the antioxidant N-Acetyl-Cysteine (NAC). In the APL NB4 model,
ASC induced direct degradation of the PML and PML/RARA proteins via caspase
activation, while the transcriptional repressor DAXX was recruited in
re-constituted PML nuclear bodies. Our findings encourage the design of pilot
studies to explore the potential clinical benefit of ASC alone or in combination
with ATO in advanced AML and APL.
|Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use
[MESH]
|Arsenic Trioxide
[MESH]
|Arsenicals/pharmacology/*therapeutic use
[MESH]
|Ascorbic Acid/pharmacology/*therapeutic use
[MESH]