NDLI: Systems biology-based discovery of a potential Atg4B agonist (Flubendazole) that induces autophagy in breast cancer.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zhang, Lan Guo, Mingrui Li, Jing Zheng, Yaxin Zhang, Shouyue Xie, Tao Liu, Bo
Description	Country affiliation: China Author Affiliation: Zhang L ( State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China. liubo2400@163.com.)
Abstract	The aim of this study was to explore the autophagy-related protein 4B(ATG4B) and its targeted candidate agonist in triple-negative breast cancer (TNBC) therapy. In this study, the identification of Atg4B as a novel breast cancer target for screening candidate small molecular agonists was performed by phylogenetic analysis, network construction, molecular modelling, molecular docking and molecular dynamics (MD) simulation. In vitro, MTT assay, electron microscopy, western blot and ROS measurement were used for validating the efficacy of the candidate compounds. We used the phylogenetic analysis of Atg4B and constructed their protein-protein interaction (PPI) network. Also, we screened target compounds of Atg4 proteins from Drugbank and ZINC. Flubendazole was validated for its anti-proliferative efficacy in MDA-MB-231 cells. Further MD simulation results supported the stable interaction between Flubendazole and Atg4B. Moreover, Flubendazole induced autophagy and increased ROS production. In conclusion, in silico analysis and experimental validation together demonstrate that Flubendazole can target Atg4B in MDA-MB-231 cells and induce autophagy, which may shed light on the exploration of this compound as a potential new Atg4B targeted drug for future TNBC therapy.
File Format	HTM / HTML
ISSN	1742206X
Issue Number	11
Volume Number	11
e-ISSN	17422051
Journal	Molecular BioSystems
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2015-11-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Discipline Molecular Biology Discipline Biochemistry Autophagy Drug Effects Breast Neoplasms Pathology Drug Discovery Mebendazole Analogs & Derivatives Systems Biology Methods Antineoplastic Agents Analysis Pharmacology Ultrastructure Cell Line, Tumor Cysteine Endopeptidases Metabolism Female Humans Molecular Docking Simulation Phylogeny Protein Interaction Mapping Reactive Oxygen Species Small Molecule Libraries Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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