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

doi:10.1155/2013/548929

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標題:	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
作者:	Wu, Chun-Chi Chen, Tzu-Hsiu Liu, Bing-Lan Wu, Li-Chen Chen, Yung-Ching Tzeng, Yew-Min Hsu, Shih-Lan
貢獻者:	保健營養系醫藥化學系
關鍵字:	Dna-Damage Response Antitumor-Activity Colorectal-Cancer Natural-Products Protein Family Cytochrome-C Cyclodepsipeptides Gefitinib Death Adenocarcinoma
日期:	2013
上傳時間:	2014-05-26 10:45:07 (UTC+8)
出版者:	Hindawi Publishing Corporation
摘要:	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.
關聯:	Evidence-Based Complementary And Alternative Medicine, v.2013, Article ID 548929
顯示於類別:	[保健營養系(所) ] 期刊論文 [食藥產業暨檢測科技系(含五專)] 期刊論文

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