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

Abstract

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.

Keywords::

• Arsenic trioxide
• aclacinomycin A
• apoptosis
• cytotoxic effect
• acute myeloid leukemia

Acknowledgements

This work was supported by the Natural Science & Technology Major Project Foundation of Zhongshan city (No. 20113A002) and Natural Science Foundation of Guangdong province (No. 2011106).

Potential conflict of interest

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Supplementary material available online

Supplementary Figures 1–2, showing further results.