Antibiotic bedaquiline effectively targets growth, survival and tumor angiogenesis of lung cancer through suppressing energy metabolism
Autor: | Xiaojiang Wang, Ziyang Zhu, Chuanhai Wang, Fajiu Li, Xiaomu Wu, Shi Chen, Qinghua Meng, Chenghong Li, Jie Huang |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Lung Neoplasms Cell Survival Angiogenesis Cell Biophysics Antineoplastic Agents Mice SCID Biology Biochemistry Metastasis Mice 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate 0302 clinical medicine Cell Line Tumor medicine Animals Humans Diarylquinolines Lung cancer Molecular Biology Cell Proliferation Matrigel Dose-Response Relationship Drug Neovascularization Pathologic Cell Biology medicine.disease Anti-Bacterial Agents Cell biology Vascular endothelial growth factor Endothelial stem cell Treatment Outcome 030104 developmental biology medicine.anatomical_structure chemistry A549 Cells 030220 oncology & carcinogenesis Cancer research Bedaquiline Energy Metabolism |
Zdroj: | Biochemical and Biophysical Research Communications. 495:267-272 |
ISSN: | 0006-291X |
Popis: | Tumor angiogenesis plays essential roles during lung cancer progression and metastasis. Therapeutic agent that targets both tumor cell and vascular endothelial cell may achieve additional anti-tumor efficacy. We demonstrate that bedaquiline, a FDA-approved antibiotic drug, effectively targets lung cancer cells and angiogenesis. Bedaquiline dose-dependently inhibits proliferation and induces apoptosis of a panel of lung cancer cell lines regardless of subtypes and molecular heterogeneity. Bedaquiline also inhibits capillary network formation of human lung tumor associated-endothelial cell (HLT-EC) on Matrigel and its multiple functions, such as spreading, proliferation and apoptosis, even in the presence of vascular endothelial growth factor (VEGF). We further demonstrate that bedaquiline acts on lung cancer cells and HLT-EC via inhibiting mitochondrial respiration and glycolysis, leading to ATP reduction and oxidative stress. Consistently, oxidative damage on DNA, protein and lipid were detected in cells exposed to bedaquiline. Importantly, the results obtained in in vitro cell culture are reproducible in in vivo xenograft lung cancer mouse model, confirming that bedaquiline suppresses lug tumor growth and angiogenesis, and increases oxidative stress. Our findings demonstrating that energy depletion is effectively against lung tumor cells and angiogenesis. Our work also provide pre-clinical evidence to repurpose antibiotic bedaquiline for lung cancer treatment. |
Databáze: | OpenAIRE |
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