Targeting Myeloperoxidase Disrupts Mitochondrial Redox Balance and Overcomes Cytarabine Resistance in Human Acute Myeloid Leukemia.
Animals
Antimetabolites, Antineoplastic
/ pharmacology
Apoptosis
Cell Line, Tumor
Cytarabine
/ pharmacology
Drug Resistance, Neoplasm
/ genetics
Gene Expression Profiling
Humans
Hypochlorous Acid
/ metabolism
Leukemia, Myeloid, Acute
/ drug therapy
Membrane Potential, Mitochondrial
Mice
Mice, Inbred NOD
Mice, SCID
Mitochondria
/ metabolism
Molecular Targeted Therapy
Neoplasm Proteins
/ antagonists & inhibitors
Oxidation-Reduction
Oxidative Stress
Peroxidase
/ antagonists & inhibitors
RNA, Neoplasm
/ biosynthesis
RNA, Small Interfering
/ genetics
Reactive Oxygen Species
Transcriptome
Xenograft Model Antitumor Assays
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
15 Oct 2019
15 Oct 2019
Historique:
received:
15
02
2019
revised:
29
05
2019
accepted:
19
07
2019
pubmed:
31
7
2019
medline:
2
6
2020
entrez:
31
7
2019
Statut:
ppublish
Résumé
Chemotherapies alter cellular redox balance and reactive oxygen species (ROS) content. Recent studies have reported that chemoresistant cells have an increased oxidative state in hematologic malignancies. In this study, we demonstrated that chemoresistant acute myeloid leukemia (AML) cells had a lower level of mitochondrial and cytosolic ROS in response to cytarabine (AraC) and overexpressed myeloperoxidase (MPO), a heme protein that converts hydrogen peroxide to hypochlorous acid (HOCl), compared with sensitive AML cells. High MPO-expressing AML cells were less sensitive to AraC
Identifiants
pubmed: 31358527
pii: 0008-5472.CAN-19-0515
doi: 10.1158/0008-5472.CAN-19-0515
doi:
Substances chimiques
Antimetabolites, Antineoplastic
0
Neoplasm Proteins
0
RNA, Neoplasm
0
RNA, Small Interfering
0
Reactive Oxygen Species
0
Cytarabine
04079A1RDZ
Hypochlorous Acid
712K4CDC10
MPO protein, human
EC 1.11.1.7
Peroxidase
EC 1.11.1.7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5191-5203Informations de copyright
©2019 American Association for Cancer Research.