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Evidence-Based Complementary and Alternative Medicine
Volume 2012, Article ID 921430, 14 pages
Research Article

Synergistic Apoptosis-Inducing Antileukemic Effects of Arsenic Trioxide and Mucuna macrocarpa Stem Extract in Human Leukemic Cells via a Reactive Oxygen Species-Dependent Mechanism

1Graduate Institute of Chinese Pharmaceutical Sciences, China Medical University, Taichung 404, Taiwan
2Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
3Center of General Education, National Taipei University of Nursing and Health Sciences, Taipei 112, Taiwan
4Department of Health and Nutrition Biotechnology, Asia University, Taichung 413, Taiwan
5Department of Nursing, Hungkuang University, Taichung 433, Taiwan
6Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 112, Taiwan
7Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan

Received 21 January 2011; Revised 10 April 2011; Accepted 17 May 2011

Academic Editor: Alfredo Vannacci

Copyright © 2012 Kuan-Hung Lu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The objective of this study was to examine the potential of enhancing the antileukemic activity of arsenic trioxide (ATO) by combining it with a folk remedy, crude methanolic extract of Mucuna macrocarpa (CMEMM). Human leukemia cells HL-60, Jurkat, and Molt-3 were treated with various doses of ATO, CMEMM, and combinations thereof for 24 and 48 h. Results indicated that the combination of 2.5 μM ATO and 50 μg/mL CMEMM synergistically inhibited cell proliferation in HL-60 and Jurkat cell lines. Apoptosis triggered by ATO/CMEMM treatment was confirmed by accumulation of cells in the sub-G1 phase in cell cycle analyses, characteristic apoptotic nuclear fragmentation, and increased percentage of annexin V-positive apoptotic cells. Such combination treatments also led to elevation of reactive oxygen species (ROS). The antioxidants N-acetyl cysteine (NAC), butylated hydroxytoluene, and α-tocopherol prevented cells from ATO/CMEMM-induced apoptosis. The ATO/CMEMM-induced activation of caspase-3 and caspase-9 can be blocked by NAC. In summary, these results suggest that ATO/CMEMM combination treatment exerts synergistic apoptosis-inducing effects in human leukemic cells through a ROS-dependent mechanism and may provide a promising antileukemic approach in the future.