title: Reactive oxygen species regulate a balance between mitotic catastrophe and apoptosis.
abstract: Mitotic catastrophe (MC) is a sequence of events resulting from premature or inappropriate entry of cells into mitosis that can be caused by chemical or physical stresses. There are several observations permitting to define MC as an oncosuppressive mechanism. MC can end up in apoptosis, necrosis or senescence. Here we show that the anticancer drug doxorubicin triggers DNA damage and MC independently of ROS production. In contrast, doxorubicin-induced apoptosis was found to be ROS-dependent. Antioxidants NAC or Trolox suppressed apoptosis, but facilitated MC development. Our data demonstrate that evasion of apoptosis and subsequent stimulation of MC can contribute to tumor cell elimination improving anticancer therapy.
authors.affiliation: Faculty of Fundamental Medicine, MV Lomonosov Moscow State University, 11999 Moscow, Russia.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Sorokina
authors.affiliation: Faculty of Fundamental Medicine, MV Lomonosov Moscow State University, 11999 Moscow, Russia.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Denisenko
authors.affiliation: Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Imreh
authors.affiliation: Faculty of Fundamental Medicine, MV Lomonosov Moscow State University, 11999 Moscow, Russia; Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Gogvadze
authors.affiliation: Faculty of Fundamental Medicine, MV Lomonosov Moscow State University, 11999 Moscow, Russia; Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden. Electronic address: Boris.Zhivotovsky@ki.se.
authors.forename: Boris
authors.initials: B
authors.lastname: Zhivotovsky
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D004317:Doxorubicin
keywords: Apoptosis; Mitochondria; Mitotic catastrophe; Reactive oxygen species; Tumor