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

• 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
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428194.2015.1011155

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.