title: Phosphonomethyl iminodiacetic acid-conjugated cobalt oxide nanoparticles liberate Co(++) ion-induced stress associated activation of TNF-α/p38 MAPK/caspase 8-caspase 3 signaling in human leukemia cells.
abstract: The aim of this work is to understand the potential health effects of metal nanoparticles by exposing human leukemic cell lines (jurkat, K562 and KG1A cells) to nanosize phosphonomethyl iminodiacetic acid coated cobalt oxide (PMIDA-CoO) NPs. The synthesized PMIDA-CoO NPs were characterized by XRD, dynamic light scattering, transmission electron microscopy and scanning electron microscopy. Our results showed that exposure of leukemic cell lines to PMIDA-CoO NPs caused reactive oxygen species (ROS) generation by increasing the concentration of free Co(++) ions in cancer microenvironment. But at physiological pH, PMIDA-CoO liberates little amount of Co(++) ions into media and exerts lower toxicity to normal cells up to a certain dose. PMIDA-CoO NPs caused DNA damage in leukemic cell lines, which was reflected by an increase in apoptosis of jurkat, KG-1A and K562 cells. PMIDA-CoO NPs induced apoptosis by increasing pro-inflammatory cytokines, primarily TNF-α. The in vivo study shows that PMIDA-CoO NPs were efficiently killed DLA cells. These findings have important implications for understanding the potential anticancer property induced by surface-modified cobalt oxide nanoparticles.
authors.affiliation: Department of Human Physiology with Community Health, Immunology and Microbiology Laboratory, Vidyasagar University, Midnapore, West Bengal, 721 102, India.
authors.forename: Sourav
authors.initials: S
authors.lastname: Chattopadhyay
authors.affiliation: Department of Human Physiology with Community Health, Immunology and Microbiology Laboratory, Vidyasagar University, Midnapore, West Bengal, 721 102, India.
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Dash
authors.affiliation: Department of Human Physiology with Community Health, Immunology and Microbiology Laboratory, Vidyasagar University, Midnapore, West Bengal, 721 102, India.
authors.forename: Satyajit
authors.initials: S
authors.lastname: Tripathy
authors.affiliation: Department of Chemistry, Nano Materials Laboratory, Indian Institute of Technology, Khargapur, West Bengal, India.
authors.forename: Panchanan
authors.initials: P
authors.lastname: Pramanik
authors.affiliation: Department of Human Physiology with Community Health, Immunology and Microbiology Laboratory, Vidyasagar University, Midnapore, West Bengal, 721 102, India. roysomenath@hotmail.com.
authors.forename: Somenath
authors.initials: S
authors.lastname: Roy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D053938:DNA Fragmentation; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007098:Imino Acids / Q000737:chemistry / Q000494:pharmacology*; D019169:Jurkat Cells; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy; D020935:MAP Kinase Signaling System; D051379:Mice; D053758:Nanoparticles; D018384:Oxidative Stress; D010087:Oxides / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D007098:Imino Acids; D010087:Oxides; D017382:Reactive Oxygen Species; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D003035:Cobalt; D048051:p38 Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; C060728:cobalt oxide