Low-Dose Arsenic Trioxide Combined with Aclacinomycin a Synergistically Enhance the Cytotoxic Effect on Human Acute Myelogenous Leukemia KG-1a Cell Line By the Induction of Apoptosis

Acute myeloid leukemia (AML) is a kind of common disorder in the elderly. Although remarkable progress has been made in the treatment of this deadly disease over the past few decades, the outcome remains poor. While conventional chemotherapy may be effective for some elderly patients, the vast majority do not tolerate intensive conventional treatment well, thus the development of a more effective method to overcome this problem is necessary. Aclacinomycin A (ACM), an antitumor antibiotic, was used to treat various tumors including AML. However, its high toxicity limits its clinical application. Previous studies reported that arsenic trioxide (As₂O₃) has shown substantial efficacy in treating patients suffering from AML. However, the molecular mechanisms of As₂O₃-induced cytotoxic effect of AML cells are not yet fully known. The aim of this study was to investigate the synergistic cytotoxic effect of low-dose As₂O₃ combined with ACM on human KG-1a cells and to clarify the possible mechanism underlying this combination treatment. Our results showed that As₂O₃ or ACM inhibited proliferation of KG-1a cells in a time- and dose-independent manner. In the flow cytometric analysis, the low-dose of the matched combination treatment induced a more prominent apoptosis than the single agent-treated groups. Furthermore, western blot analysis showed that the combination treatment decreased Bcl-2 expression and increased caspase-3 expression more significantly than the single drug treatments. More importantly, we showed that the combination index (CI) values were < 1 in all matched combination groups analyzed by compusyn software. In conclusion, our data showed that low-dose As₂O₃ combined with ACM showed a more prominent cytotoxic effect than single agent treatment on KG-1a cells. These results may provide a high efficiency but low-toxicity therapeutic benefits for AML.