Boris Ivanovas

Publications (2)7.43 Total impact

• Article: Nitric oxide mediates apoptosis induction selectively in transformed fibroblasts compared to nontransformed fibroblasts.

  Stefanie Heigold, Christine Sers, Wibke Bechtel, Boris Ivanovas, Reinhold Schäfer, Georg Bauer
  [show abstract] [hide abstract]
  ABSTRACT: Nitric oxide (NO) mediates apoptosis induction in fibroblasts with constitutive src or induced ras oncogene expression, whereas nontransformed parental cells and revertants are not affected. This direct link between the transformed phenotype and sensitivity to NO-mediated apoptosis induction seems to be based on the recently described extracellular superoxide anion generation by transformed cells, as NO-mediated apoptosis induction in transformed cells is inhibited by extracellular superoxide dismutase (SOD), by SOD mimetics and by apocynin, an inhibitor of NADPH oxidase. Furthermore, nonresponsive nontransformed cells can be rendered sensitive for NO-mediated apoptosis induction when they are supplemented with xanthine oxidase/xanthine as an extracellular source for superoxide anions. As superoxide anions and NO readily interact in a diffusion-controlled reaction to generate peroxynitrite, peroxynitrite seems to be the responsible apoptosis inducer in NO-mediated apoptosis induction. In line with this conclusion, NO-mediated apoptosis induction in superoxide anion-generating transformed cells is inhibited by the peroxynitrite scavengers ebselen and FeTPPS. Moreover, direct application of peroxynitrite induces apoptosis both in transformed and nontransformed cells, indicating that peroxynitrite is no selective apoptosis inducer per se, but that selective apoptosis induction in transformed cells by NO is achieved through selective peroxynitrite generation. The interaction of NO with target cell derived superoxide anions represents a novel concept for selective apoptosis induction in transformed cells. This mechanism may be the basis for selective apoptosis induction by natural antitumor systems (like macrophages, natural killer cells, granulocytes) that utilize NO for antitumor action. Apoptosis induction mediated by NO involves mitochondrial depolarization and is blocked by Bcl-2 overexpression.
  Carcinogenesis 07/2002; 23(6):929-41. · 5.70 Impact Factor
• Article: Selective and non-selective apoptosis induction in transformed and non-transformed fibroblasts by exogenous reactive oxygen and nitrogen species.

  Boris Ivanovas, Alf Zerweck, Georg Bauer
  [show abstract] [hide abstract]
  ABSTRACT: This paper defines selective and nonselective apoptosis induction in transformed and nontransformed fibroblasts by extracellular reactive oxygen and nitrogen species (ROS and RNS). Superoxide anions do not exhibit direct apoptosis inducing potential, whereas their dismutation product hydrogen peroxide induces apoptosis nonselectively in transformed and nontransformed fibroblasts. Myeloperoxidase converts hydrogen peroxide into the selective apoptosis mediator HOCl, which interacts with transformed target cell-derived superoxide anions and generates apoptosis-inducing hydroxyl radicals. Nitric oxide does not induce apoptosis directly in fibroblasts. However, interaction of nitric oxide with transformed cell-derived superoxide anions leads to the generation of the ultimate apoptosis inducer, peroxynitrite. Peroxynitrite by itself does not discriminate between transformed and nontransformed cells. The direction of generation of apoptosis inducing ROS and RNS to the site of superoxide anion production has relevance for the selectivity of ROS and RNS-based natural antitumor systems, as extracellular superoxide anion generation represents a hallmark of the transformed state.
  Anticancer research 22(2A):841-56. · 1.73 Impact Factor