Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2013, Article ID 548929, 11 pages http://dx.doi.org/10.1155/2013/548929 Research Article Destruxin B Isolated from Entomopathogenic Fungus Metarhizium anisopliae Induces Apoptosis via a Bcl-2 Family-Dependent Mitochondrial Pathway in Human Nonsmall Cell Lung Cancer Cells Chun-Chi Wu, 1,2 Tzu-Hsiu Chen, 3 Bing-Lan Liu, 4 Li-Chen Wu, 5 Yung-Ching Chen, 1 Yew-Min Tzeng, 4 and Shih-Lan Hsu 1,6 1 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan 2 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan 3 Department of Health and Nutrition, Chia Nan University of Pharmacy & Science, Tainan, Taiwan 4 Department of Applied Chemistry, Chaoyang University of Technology, Taichung, Taiwan 5 Department of Applied Chemistry, National Chi Nan University, Puli, Nantou, Taiwan 6 Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan Correspondence should be addressed to Yew-Min Tzeng; ymtzeng@cyut.edu.tw and Shih-Lan Hsu; h2326@vghtc.gov.tw Received 20 March 2013; Accepted 20 August 2013 Academic Editor: Mei Tian Copyright © 2013 Chun-Chi Wu et al. Tis 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. Destruxin B, isolated from entomopathogenic fungus Metarhizium anisopliae, is one of the cyclodepsipeptides with insecticidal and anticancer activities. In this study, destruxin B was extracted and purifed by ion-exchange chromatography, silica gel chromatography, and semipreparative high-performance liquid chromatography. Te potential anticancer efects and molecular mechanisms of destruxin B in human nonsmall cell lung cancer cell lines were characterized. Our results showed that destruxin B induced apoptotic cell death in A549 cells. Tis event was accompanied by the activation of caspase-2, -3, and -9. Moreover, destruxin B increased the expression level of proapoptotic molecule, PUMA, while decreased antiapoptotic molecule Mcl-1. Additionally, the translocation of Bax from cytosol to mitochondrial membrane was observed upon destruxin B treatment. Knockdown of Bax by shRNA efectively attenuated destruxin-B-triggered apoptosis in A549 cells. Interestingly, similar toxic efects and underlying mechanisms including caspase activation, upregulation of PUMA, and downregulation of Mcl-1 were also observed in a p53-null lung cancer H1299 cell line upon destruxin B treatment. Taken together, our fndings suggest that destruxin-B-induced apoptosis in human nonsmall cell lung cancer cells is via a Bcl-2 family-dependent mitochondrial pathway. 1. Introduction Lung cancer is the leading cause of death for both men and women in many countries, including Taiwan, which exhibited the highest rate of increase in lung cancer mortality in recent years [1, 2]. Te fve-year survival rate of lung cancer patient is only 13–25% [3]. Although target therapy emerged for treatment of lung cancer patients in the past decade [4], there is still a large amount of patients who are uncured. It appears that the drugs with greater efcacy than existing treatments are urgently required for these patients. Growing evidence demonstrates that apoptosis is involved in many biological events including physiological homeostasis and embryogenesis [5] and is also an important determinant of the response of cancers to chemo-, radiation, or target-therapy [6, 7]; compounds that induce these events may provide potent anticancer efects for cancer treatment. Te regulatory mechanisms of apoptosis are quite complicated networks. Two major types of apoptosis pathways are mentioned: one is the intrinsic pathway which is mediated by the regulators located in the mitochondrial [8] and the other is the extrinsic pathway which is regulated