title: Ferroferric oxide nanoparticles induce prosurvival autophagy in human blood cells by modulating the Beclin 1/Bcl-2/VPS34 complex.
abstract: Magnetic iron oxide nanoparticles (NPs) are emerging as novel materials with great potentials for various biomedical applications, but their biological activities are largely unknown. In the present study, we found that ferroferric oxide nanoparticles (Fe3O4 NPs) induced autophagy in blood cells. Both naked and modified Fe3O4 NPs induced LC3 lipidation and degraded p62, a monitor of autophagy flux. And this change could be abolished by autophagy inhibitors. Mechanistically, Fe3O4 NP-induced autophagy was accompanied by increased Beclin 1 and VPS34 and decreased Bcl-2, thus promoting the formation of the critical complex in autophagy initiation. Further studies demonstrated that Fe3O4 NPs attenuated cell death induced by anticancer drugs bortezomib and doxorubicin. Therefore, this study suggested that Fe3O4 NPs can induce prosurvival autophagy in blood cells by modulating the Beclin l/Bcl-2/VPS34 complex. This study suggests that caution should be taken when Fe3O4 NPs are used in blood cancer patients.
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Functional Nano and Soft Material (FUNSOM), Collaborative Innovation Center of Suzhou, Nano Science and Technology, Soochow University, Suzhou, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
authors.forename: Zubin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Functional Nano and Soft Material (FUNSOM), Collaborative Innovation Center of Suzhou, Nano Science and Technology, Soochow University, Suzhou, People's Republic of China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China ; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, People's Republic of China.
authors.forename: Xinliang
authors.initials: X
authors.lastname: Mao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D001773:Blood Cells / Q000187:drug effects* / Q000378:metabolism; D000069286:Bortezomib / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D005290:Ferric Compounds / Q000737:chemistry* / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; C000595707:BCL2 protein, human; C491997:BECN1 protein, human; D000071186:Beclin-1; D005290:Ferric Compounds; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C000499:ferric oxide; D000069286:Bortezomib; D004317:Doxorubicin
keywords: anti-apoptosis; autophagic pathway; iron oxide nanoparticle