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Evidence-Based Complementary and Alternative Medicine
Volume 2012, Article ID 201414, 11 pages
http://dx.doi.org/10.1155/2012/201414
Research Article

Tetraarsenic Hexoxide Induces Beclin-1-Induced Autophagic Cell Death as well as Caspase-Dependent Apoptosis in U937 Human Leukemic Cells

1Department of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control (BK21 Program), Dongeui University Graduate School, 42 San, Yangjung-don, Busan 614-052, Republic of Korea
2Department of Internal Medicine, Institute of Health Sciences and Gyeongnam Regional Cancer Center, Gyeongsang National University School of Medicine, 90 Chilam-dong, Jinju 660-702, Republic of Korea
3Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea
4Institute of Life Science and School of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea
5Department of Neurosurgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Republic of Korea
6Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea
7Department of Chemistry, Hanyang University, Seoul 133-791, Republic of Korea
8Department of Urology, Chungbuk National University College of Medicine, Cheongju, Chungbuk 361-763, Republic of Korea

Received 7 May 2011; Revised 24 June 2011; Accepted 24 June 2011

Academic Editor: Shrikant Anant

Copyright © 2012 Min Ho Han 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.

Abstract

Tetraarsenic hexaoxide (As4O6) has been used in Korean folk remedy for the treatment of cancer since the late 1980s, and arsenic trioxide (As2O3) is currently used as a chemotherapeutic agent. However, evidence suggests that As4O6-induced cell death pathway was different from that of As2O3. Besides, the anticancer effects and mechanisms of As4O6 are not fully understood. Therefore, we investigated the anticancer activities of As4O6 on apoptosis and autophagy in U937 human leukemic cells. The growth of U937 cells was inhibited by As4O6 treatment in a dose- and a time-dependent manner, and IC50 for As4O6 was less than 2 μM. As4O6 induced caspase-dependent apoptosis and Beclin-1-induced autophagy, both of which were significantly attenuated by Bcl-2 augmentation and N-acetylcysteine (NAC) treatment. This study suggests that As4O6 should induce Beclin-1-induced autophagic cell death as well as caspase-dependent apoptosis and that it might be a promising agent for the treatment of leukemia.