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Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 828143, 15 pages
http://dx.doi.org/10.1155/2013/828143
Research Article

Subamolide A Induces Mitotic Catastrophe Accompanied by Apoptosis in Human Lung Cancer Cells

1Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
2Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 801, Taiwan
3Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
4Department of Beauty Science, National Taichung University of Science and Technology, Taichung 403, Taiwan
5School of Medical and Health Sciences, Fooyin University, Kaohsiung 831, Taiwan
6Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
7Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
8Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

Received 12 September 2012; Revised 28 December 2012; Accepted 23 January 2013

Academic Editor: Seung-Heon Hong

Copyright © 2013 Jen-Yu Hung 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

This study investigated the anticancer effects of subamolide A (Sub-A), isolated from Cinnamomum subavenium, on human nonsmall cell lung cancer cell lines A549 and NCI-H460. Treatment of cancer cells with Sub-A resulted in decreased cell viability of both lung cancer cell lines. Sub-A induced lung cancer cell death by triggering mitotic catastrophe with apoptosis. It triggered oxidant stress, indicated by increased cellular reactive oxygen species (ROS) production and decreased glutathione level. The elevated ROS triggered the activation of ataxia-telangiectasia mutation (ATM), which further enhanced the ATF3 upregulation and subsequently enhanced p53 function by phosphorylation at Serine 15 and Serine 392. The antioxidant, EUK8, significantly decreased mitotic catastrophe by inhibiting ATM activation, ATF3 expression, and p53 phosphorylation. The reduction of ATM and ATF3 expression by shRNA decreased Sub-A-mediated p53 phosphorylation and mitotic catastrophe. Sub-A also caused a dramatic 70% reduction in tumor size in an animal model. Taken together, cell death of lung cancer cells in response to Sub-A is dependent on ROS generation, which triggers mitotic catastrophe followed by apoptosis. Therefore, Sub-A may be a novel anticancer agent for the treatment of nonsmall cell lung cancer.