title: Reactive Oxygen Species Synergize To Potently and Selectively Induce Cancer Cell Death.
abstract: A distinctive feature of cancer cells is their elevated levels of reactive oxygen species (ROS), a trait that can cause cancer cells to be more sensitive to ROS-inducing agents than normal cells. ROS take several forms, each with different reactivity and downstream consequence. Here we show that simultaneous generation of superoxide and hydrogen peroxide within cancer cells results in significant synergy, potently and selectively causing cancer cell death. In these experiments superoxide is generated using the NAD(P)H quinone oxidoreductase 1 (NQO1) substrate deoxynyboquinone (DNQ), and hydrogen peroxide is generated using the lactate dehydrogenase A (LDH-A) inhibitor NHI-Glc-2. This combination reduces tumor burden and prolongs survival in a mouse model of lung cancer. These data suggest that simultaneous induction of superoxide and hydrogen peroxide can be a powerful and selective anticancer strategy.
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Hyang Yeon
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Elizabeth I
authors.initials: EI
authors.lastname: Parkinson
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , Via Bonanno 33, 56126 Pisa, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Granchi
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , Via Bonanno 33, 56126 Pisa, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Paterni
authors.forename: Dipak
authors.initials: D
authors.lastname: Panigrahy
authors.forename: Pankaj
authors.initials: P
authors.lastname: Seth
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , Via Bonanno 33, 56126 Pisa, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Minutolo
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Paul J
authors.identifier: 0000-0001-9018-3581
authors.initials: PJ
authors.lastname: Hergenrother
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004357:Drug Synergism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors; D000080864:Lactate Dehydrogenase 5; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D013481:Superoxides / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D017382:Reactive Oxygen Species; D013481:Superoxides; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5