title: 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.
abstract: 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.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan ; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Wu
authors.forename: Tzu-Hsiu
authors.initials: TH
authors.lastname: Chen
authors.forename: Bing-Lan
authors.initials: BL
authors.lastname: Liu
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Wu
authors.forename: Yung-Ching
authors.initials: YC
authors.lastname: Chen
authors.forename: Yew-Min
authors.initials: YM
authors.lastname: Tzeng
authors.forename: Shih-Lan
authors.initials: SL
authors.lastname: Hsu