title: Effect of platinum nanoparticles on cell death induced by ultrasound in human lymphoma U937 cells.
abstract: In this study, we report on the potential use of platinum nanoparticles (Pt-NPs), a superoxide dismutase (SOD)/catalase mimetic antioxidant, in combination with 1MHz ultrasound (US) at an intensity of 0.4 W/cm(2), 10% duty factor, 100 Hz PRF, for 2 min. Apoptosis induction was assessed by DNA fragmentation assay, cell cycle analysis and Annexin V-FITC/PI staining. Cell killing was confirmed by cell counting and microscopic examination. The mitochondrial and Ca(2+)-dependent pathways were investigated. Caspase-8 expression and autophagy-related proteins were detected by spectrophotometry and western blot analysis, respectively. Intracellular reactive oxygen species (ROS) elevation was detected by flow cytometry, while extracellular free radical formation was assessed by electron paramagnetic resonance spin trapping spectrometry. The results showed that Pt-NPs exerted differential effects depending on their internalization. Pt-NPs functioned as potent free radical scavengers when added immediately before sonication while pre-treatment with Pt-NPs suppressed the induction of apoptosis as well as autophagy (AP), and resulted in enhanced cell killing. Dead cells displayed the features of pyknosis. The exact mode of cell death is still unclear. In conclusion, the results indicate that US-induced AP may contribute to cell survival post sonication. To our knowledge this is the first study to discuss autophagy as a pro-survival pathway in the context of US. The combination of Pt-NPs and US might be effective in cancer eradication.
authors.affiliation: Department of Radiological Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Paras
authors.initials: P
authors.lastname: Jawaid
authors.affiliation: Department of Radiological Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Mati Ur
authors.initials: MU
authors.lastname: Rehman
authors.affiliation: Department of Radiological Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; Department of Pharmaceutics & Pharmaceutical Technology, University of Sharjah, Sharjah, United Arab Emirates; Department of Pharmaceutics & Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Mariame Ali
authors.initials: MA
authors.lastname: Hassan
authors.affiliation: Department of Radiological Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Qing Li
authors.initials: QL
authors.lastname: Zhao
authors.affiliation: Department of Radiological Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Yusei
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Institute for Human Science and Biomedical Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Misawa
authors.affiliation: Department of Radiological Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Ogawa
authors.affiliation: Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Radiological Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. Electronic address: kondot@med.u-toyama.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006801:Humans; D008223:Lymphoma / Q000473:pathology*; D053768:Metal Nanoparticles; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology*; D020298:U937 Cells
chemical_list: D010984:Platinum
keywords: Apoptosis; Autophagy; Necroptosis; Platinum nanoparticles; Reactive oxygen species; Ultrasound