Targeting catalase but not peroxiredoxins enhances arsenic trioxide-induced apoptosis in K562 cells

Li-Li Song; Yao-Yao Tu; Li Xia; Wei-Wei Wang; Wei Wei; Chun-Min Ma; Dong-Hua Wen; Hu Lei; Han-Zhang Xu; Ying-Li Wu

doi:10.1371/journal.pone.0104985

Targeting catalase but not peroxiredoxins enhances arsenic trioxide-induced apoptosis in K562 cells

PLoS One. 2014 Aug 12;9(8):e104985. doi: 10.1371/journal.pone.0104985. eCollection 2014.

Authors

Li-Li Song¹, Yao-Yao Tu¹, Li Xia¹, Wei-Wei Wang¹, Wei Wei¹, Chun-Min Ma¹, Dong-Hua Wen¹, Hu Lei¹, Han-Zhang Xu¹, Ying-Li Wu¹

Affiliation

¹ Department of Pathophysiology, Chemical Biology Division of Shanghai Universities E-Institutes, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology
Apoptosis / drug effects*
Apoptosis / genetics
Apoptosis / physiology
Arsenic Trioxide
Arsenicals / pharmacology*
Catalase / antagonists & inhibitors*
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
Oxides / pharmacology*
Peroxiredoxins / antagonists & inhibitors*
Peroxiredoxins / genetics
Peroxiredoxins / metabolism
Reactive Oxygen Species / metabolism

Substances

Antineoplastic Agents
Arsenicals
Oxides
Reactive Oxygen Species
Peroxiredoxins
Catalase
Fusion Proteins, bcr-abl
Arsenic Trioxide

Grants and funding

This work was supported in part by grants from National Basic Research Program of China (973 Program) (NO. 2010CB912104), National Natural Science Foundation of China (91313303, 81272886, 31100980), Science and Technology Committee of Shanghai (11JC1406500), Shanghai Talent Development Project of Shanghai Human Resource and Social Security Bureau. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.