title: Overendocytosis of superparamagnetic iron oxide particles increases apoptosis and triggers autophagic cell death in human osteosarcoma cell under a spinning magnetic field.
abstract: The toxicity of superparamagnetic iron oxide nanoparticles (SPIONs) is still a vital topic of debate and the mechanisms remain unclear. In the present study, overdose SPIONs could induce osteosarcoma cell death and the effects were exaggerated when combined with spinning magnetic field (SMF). In the combination group, mitochondrial transmembrane potential decrease more obviously and reactive oxygen species (ROS) was found to generate much higher in line with that of the apoptosis ratio. Meantime, amount of autophagy was induced. Inhibiting the autophagy generation by 3-methyladenine (3-MA) increase cell viability but decrease the caspase 3/7 and caspase 8 activities in combination groups, and inhibiting apoptosis took the same effect. In the end, the SPIONs effects on xenograft mice was examed by intratumoral injection. The result showed that the combination group could greatly decrease the tumor volume and prolong the lifespan of mice. In sum, the result indicated that overdose SPIONs induced ROS generation, and excessive ROS induced by combination of SPIONs and SMF contribute to autophagy formation, which play a apoptosis-promoting role that formed as a platform to recruits initiate the caspase activities.
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310008, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Du
authors.affiliation: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Jingxiong
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Economics, Dongbei University of Finance and Economics, Dalian, 116025, China.
authors.forename: Chonghua
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Orthopaedic Surgery, Xiaoshan Chinese Medical Hospital, Hangzhou, 311201, China.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310008, China.
authors.forename: Guangnan
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310008, China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Yan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D052203:Ferrosoferric Oxide / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D055909:Magnetic Field Therapy / Q000379:methods*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D020169:Caspases; D052203:Ferrosoferric Oxide
keywords: apoptosis; autophagy; osteosarcoma; spinning magnetic field; superparamagnetic iron oxide particles