title: Growth arrest of lung carcinoma cells (A549) by polyacrylate-anchored peroxovanadate by activating Rac1-NADPH oxidase signalling axis.
abstract: Hydrogen peroxide is often required in sublethal, millimolar concentrations to show its oxidant effects on cells in culture as it is easily destroyed by cellular catalase. Previously, we had shown that diperoxovanadate, a physiologically stable peroxovanadium compound, can substitute H2O2 effectively in peroxidation reactions. We report here that peroxovanadate when anchored to polyacrylic acid (PAPV) becomes a highly potent inhibitor of growth of lung carcinoma cells (A549). The early events associated with PAPV treatment included cytoskeletal modifications, increase in GTPase activity of Rac1, accumulation of the reactive oxygen species, and also increase in phosphorylation of H2AX (γH2AX), a marker of DNA damage. These effects persisted even at 24 h after removal of the compound and culminated in increased levels of p53 and p21 together with growth arrest. The PAPV-mediated growth arrest was significantly abrogated in cells pre-treated with the N-acetylcysteine, Rac1 knocked down by siRNA and DPI an inhibitor of NADPH oxidase. In conclusion, our results show that polyacrylate derivative of peroxovanadate efficiently arrests growth of A549 cancerous cells by activating the axis of Rac1-NADPH oxidase leading to oxidative stress and DNA damage.
authors.affiliation: Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, 500001, India. neeru75@gmail.com.
authors.forename: Nirupama
authors.initials: N
authors.lastname: Chatterjee
authors.affiliation: Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, 500001, India.|Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India.|Graduate Studies, Manipal University, Manipal, 576104, India.
authors.forename: Tarique
authors.initials: T
authors.lastname: Anwar
authors.affiliation: Department of Chemical Sciences, Tezpur University, Tezpur, Assam, 784028, India.
authors.forename: Nashreen S
authors.initials: NS
authors.lastname: Islam
authors.affiliation: Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, 500001, India.|Indian Institute of Science, Bangalore, 560012, India.
authors.forename: T
authors.initials: T
authors.lastname: Ramasarma
authors.affiliation: Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad, 500001, India. gayatrirama1@gmail.com.|Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India. gayatrirama1@gmail.com.
authors.forename: Gayatri
authors.initials: G
authors.lastname: Ramakrishna
mesh_terms: D000180:Acrylic Resins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004249:DNA Damage; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D014638:Vanadates / Q000494:pharmacology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000180:Acrylic Resins; D009363:Neoplasm Proteins; C107953:RAC1 protein, human; C069276:peroxovanadate; D014638:Vanadates; C006903:carbopol 940; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D020830:rac1 GTP-Binding Protein
keywords: Peroxovanadate; Rac1; Reactive oxygen species; Senescence