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

• Published in: Evidence-based complementary and alternative medicine Vol. 2013; no. 2013; pp. 1 - 11
• Main Authors: Wu, Chun-Chi, Chen, Tzu-Hsiu, Liu, Bing-Lan, Wu, Li-Chen, Chen, Yung-Ching, Tzeng, Yew-Min, Hsu, Shih-Lan
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Puplishing Corporation 01.01.2013; Hindawi Publishing Corporation; Hindawi Limited
• Subjects: Activation; Apoptosis; Bcl-2 protein; Cancer therapies; Caspase; Caspase-2; Cell death; Cell lines; Chromatography; Colorectal cancer; Cytochrome; Cytosol; Entomopathogenic fungi; Fungi; Gel chromatography; High performance liquid chromatography; Ion-exchange chromatography; Liquid chromatography; Lung cancer; Lungs; Lymphocytes B; Mcl-1 protein; Metarhizium anisopliae; Mitochondria; Molecular modelling; p53 Protein; Proteins; Silica; Silica gel; Toxicity; Translocation; Tumor cell lines; Tumor necrosis factor-TNF; United Kingdom > UK; United States > US
• ISSN: 1741-427X; 1741-4288
• DOI: 10.1155/2013/548929

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 purified by ion-exchange chromatography, silica gel chromatography, and semipreparative high-performance liquid chromatography. The potential anticancer effects 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. This 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 effectively attenuated destruxin-B-triggered apoptosis in A549 cells. Interestingly, similar toxic effects 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 findings suggest that destruxin-B-induced apoptosis in human nonsmall cell lung cancer cells is via a Bcl-2 family-dependent mitochondrial pathway.