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Targeting catalase but not peroxiredoxins enhances arsenic trioxide-induced apoptosis in K562 cells.
- Source :
-
PloS one [PLoS One] 2014 Aug 12; Vol. 9 (8), pp. e104985. Date of Electronic Publication: 2014 Aug 12 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- Despite considerable efficacy of arsenic trioxide (As2O3) in acute promyelocytic leukemia (APL) treatment, other non-APL leukemias, such as chronic myeloid leukemia (CML), are less sensitive to As2O3 treatment. However, the underlying mechanism is not well understood. Here we show that relative As2O3-resistant K562 cells have significantly lower ROS levels than As2O3-sensitive NB4 cells. We compared the expression of several antioxidant enzymes in these two cell lines and found that peroxiredoxin 1/2/6 and catalase are expressed at high levels in K562 cells. We further investigated the possible role of peroxirdoxin 1/2/6 and catalase in determining the cellular sensitivity to As2O3. Interestingly, knockdown of peroxiredoxin 1/2/6 did not increase the susceptibility of K562 cells to As2O3. On the contrary, knockdown of catalase markedly enhanced As2O3-induced apoptosis. In addition, we provide evidence that overexpression of BCR/ABL cannot increase the expression of PRDX 1/2/6 and catalase. The current study reveals that the functional role of antioxidant enzymes is cellular context and treatment agents dependent; targeting catalase may represent a novel strategy to improve the efficacy of As2O3 in CML treatment.
- Subjects :
- Antineoplastic Agents pharmacology
Apoptosis genetics
Apoptosis physiology
Arsenic Trioxide
Catalase genetics
Catalase metabolism
Cell Line, Tumor
Fusion Proteins, bcr-abl genetics
Fusion Proteins, bcr-abl metabolism
Gene Knockdown Techniques
Humans
K562 Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism
Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology
Leukemia, Promyelocytic, Acute drug therapy
Leukemia, Promyelocytic, Acute metabolism
Leukemia, Promyelocytic, Acute pathology
Peroxiredoxins genetics
Peroxiredoxins metabolism
Reactive Oxygen Species metabolism
Apoptosis drug effects
Arsenicals pharmacology
Catalase antagonists & inhibitors
Oxides pharmacology
Peroxiredoxins antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 25115845
- Full Text :
- https://doi.org/10.1371/journal.pone.0104985