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 cytotoxic effect of low-dose arsenic trioxide (As2O3) 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 As2O3 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 As2O3 combined with ACM as a potential therapeutic benefit for AML seems warranted.
a Department of Hematology , Zhujiang Hospital, Southern Medical University , Guangzhou , China.
Yongbin
Y
Ye
b Department of Hematology , Zhongshan Hospital Affiliated to Sun Yat-Sen University , Zhongshan , China.
Xiaojun
X
Xu
a Department of Hematology , Zhujiang Hospital, Southern Medical University , Guangzhou , China.
Mingwan
M
Zhang
b Department of Hematology , Zhongshan Hospital Affiliated to Sun Yat-Sen University , Zhongshan , China.
Dafa
D
Qiu
c Department of Cell Biology , Southern Medical University , Guangzhou , China.
Xiaochun
X
Bai
a Department of Hematology , Zhujiang Hospital, Southern Medical University , Guangzhou , China.
Jing
J
Wang
a Department of Hematology , Zhujiang Hospital, Southern Medical University , Guangzhou , China.
Guangyang
G
Weng
b Department of Hematology , Zhongshan Hospital Affiliated to Sun Yat-Sen University , Zhongshan , China.
Ruiqing
R
Zhou
b Department of Hematology , Zhongshan Hospital Affiliated to Sun Yat-Sen University , Zhongshan , China.
Ziwen
Z
Guo
b Department of Hematology , Zhongshan Hospital Affiliated to Sun Yat-Sen University , Zhongshan , China.
Huiqing
H
He
a Department of Hematology , Zhujiang Hospital, Southern Medical University , Guangzhou , China.
Wenfang
W
Yi
a Department of Hematology , Zhujiang Hospital, Southern Medical University , Guangzhou , China.
Xin
X
He
a Department of Hematology , Zhujiang Hospital, Southern Medical University , Guangzhou , China.
Kunyuan
K
Guo
D015250:Aclarubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015870:Gene Expression; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001152:Arsenicals; D010087:Oxides; C011157:aclacinomycins; D015250:Aclarubicin; D000077237:Arsenic Trioxide
Arsenic trioxide; aclacinomycin A; acute myeloid leukemia; apoptosis; cytotoxic effect