Low-dose arsenic trioxide combined with aclacinomycin A synergistically enhances the cytotoxic effect on human acute myelogenous leukemia cell lines by induction of apoptosis

Acute myeloid leukemia (AML) is a common disorder in the elderly. Although remarkable progress has been made over recent decades, the outcome remains poor. Thus, the development of a more effective method to overcome this problem is necessary. In this study, we aimed to investigate the synergistic c...

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Bibliographic Details
Published in:Leukemia & lymphoma 2015-11, Vol.56 (11), p.3159-3167
Main Authors: Ye, Yongbin, Xu, Xiaojun, Zhang, Mingwan, Qiu, Dafa, Bai, Xiaochun, Wang, Jing, Weng, Guangyang, Zhou, Ruiqing, Guo, Ziwen, He, Huiqing, Yi, Wenfang, He, Xin, Guo, Kunyuan
Format: Article
Language:English
Subjects:
aclacinomycin A
Aclarubicin - analogs & derivatives
Aclarubicin - pharmacology
acute myeloid leukemia
Antineoplastic Agents - pharmacology
apoptosis
Apoptosis - drug effects
Apoptosis Regulatory Proteins - genetics
Apoptosis Regulatory Proteins - metabolism
Arsenic Trioxide
Arsenicals - pharmacology
Cell Cycle - drug effects
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Survival - drug effects
cytotoxic effect
Dose-Response Relationship, Drug
Drug Synergism
Gene Expression
HL-60 Cells
Humans
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - metabolism
Oxides - pharmacology
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Summary:Acute myeloid leukemia (AML) is a common disorder in the elderly. Although remarkable progress has been made over recent decades, the outcome remains poor. Thus, the development of a more effective method to overcome this problem is necessary. In this study, we aimed to investigate the synergistic cytotoxic effect of low-dose arsenic trioxide (As 2 O 3 ) combined with aclacinomycin A (ACM) on the human AML cell lines KG-1a and HL-60, and to clarify the underlying mechanism. Results showed that As 2 O 3 combined with ACM exerted a synergistic cytotoxic effect by activation of the apoptosis pathway. Additionally, we found that the combination treatment decreased Bcl-2, c-IAP and XIAP expression but increased SMAC and caspase-3 expression more significantly than the single drug treatments. Furthermore, combination index (CI) values were < 1 in all matched combination groups. Additional evaluation of As 2 O 3 combined with ACM as a potential therapeutic benefit for AML seems warranted.
ISSN:1042-8194
1029-2403
DOI:10.3109/10428194.2015.1011155