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
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-performan...
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doaj-dedeba55ff9e4c18a549e8d0f71c869f2020-11-25T00:53:13ZengHindawi LimitedEvidence-Based Complementary and Alternative Medicine1741-427X1741-42882013-01-01201310.1155/2013/548929548929Destruxin B Isolated from Entomopathogenic Fungus Metarhizium anisopliae Induces Apoptosis via a Bcl-2 Family-Dependent Mitochondrial Pathway in Human Nonsmall Cell Lung Cancer CellsChun-Chi Wu0Tzu-Hsiu Chen1Bing-Lan Liu2Li-Chen Wu3Yung-Ching Chen4Yew-Min Tzeng5Shih-Lan Hsu6Institute of Medicine, Chung Shan Medical University, Taichung, TaiwanDepartment of Health and Nutrition, Chia Nan University of Pharmacy & Science, Tainan, TaiwanDepartment of Applied Chemistry, Chaoyang University of Technology, Taichung, TaiwanDepartment of Applied Chemistry, National Chi Nan University, Puli, Nantou, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung, TaiwanDepartment of Applied Chemistry, Chaoyang University of Technology, Taichung, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung, TaiwanDestruxin 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.http://dx.doi.org/10.1155/2013/548929 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chun-Chi Wu Tzu-Hsiu Chen Bing-Lan Liu Li-Chen Wu Yung-Ching Chen Yew-Min Tzeng Shih-Lan Hsu |
spellingShingle |
Chun-Chi Wu Tzu-Hsiu Chen Bing-Lan Liu Li-Chen Wu Yung-Ching Chen Yew-Min Tzeng Shih-Lan Hsu 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 Evidence-Based Complementary and Alternative Medicine |
author_facet |
Chun-Chi Wu Tzu-Hsiu Chen Bing-Lan Liu Li-Chen Wu Yung-Ching Chen Yew-Min Tzeng Shih-Lan Hsu |
author_sort |
Chun-Chi Wu |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Hindawi Limited |
series |
Evidence-Based Complementary and Alternative Medicine |
issn |
1741-427X 1741-4288 |
publishDate |
2013-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2013/548929 |
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