title: Photocytotoxic effect of C60 fullerene against L1210 leukemic cells is accompanied by enhanced nitric oxide production and p38 MAPK activation.
abstract: OBJECTIVE
  To estimate the combined action of C60 fullerene and light irradiation on viability of L1210 leukemic cells, nitric oxide (NO) generation, p38 mitogen-activated protein kinase (MAPK) activity and cell cycle distribution.
  
  
  METHODS
  Cell viability was assessed by MTT test. Light-emitting diode lamp (λ = 410-700 nm, 2.45 J/cm(2) ) was used for C60 fullerene photoexcitation. Nitrite level and NO-synthase activity were measured by Griess reaction and by conversion of L-arginine to L-citrulline, respectively. p38 MAPK activity was assessed by Western blot analysis. Cell cycle distribution was determined by flow cytometry.
  
  
  RESULTS
  It was shown that light irradiation of C60 fullerene-treated L1210 cells was accompanied by 55% decrease of their viability at 48 h of culture. Nitrite level measured as an index of reactive NO generation was increased at the early period after C60 fullerene photoexcitation due to activation of both constitutive and inducible NO-synthase isoforms. The simultaneous activation of p38 MAPK was detected. Accumulation of L1210 cells in sub-G1 phase of cell cycle was observed after C60 fullerene photoexcitation.
  
  
  CONCLUSIONS
  Photoexcited C60 fullerene exerts cytotoxic effect, at least in part, through triggering production of reactive NO species and activation of p38 kinase apoptotic pathways in L1210 leukemic cells.
authors.forename: D V
authors.initials: DV
authors.lastname: Franskevych
authors.affiliation: Taras Shevchenko National University of Kyiv, Kyiv 01601, Ukraine.
authors.forename: I I
authors.initials: II
authors.lastname: Grynyuk
authors.affiliation: Taras Shevchenko National University of Kyiv, Kyiv 01601, Ukraine.
authors.forename: S V
authors.initials: SV
authors.lastname: Prylutska
authors.affiliation: Palladin Institute of Biochemistry, NAS of Ukraine, Kyiv 01011, Ukraine.
authors.forename: G V
authors.initials: GV
authors.lastname: Pasichnyk
authors.affiliation: Palladin Institute of Biochemistry, NAS of Ukraine, Kyiv 01011, Ukraine.
authors.forename: D M
authors.initials: DM
authors.lastname: Petukhov
authors.affiliation: Palladin Institute of Biochemistry, NAS of Ukraine, Kyiv 01011, Ukraine.
authors.forename: L B
authors.initials: LB
authors.lastname: Drobot
authors.affiliation: Taras Shevchenko National University of Kyiv, Kyiv 01601, Ukraine.
authors.forename: O P
authors.initials: OP
authors.lastname: Matyshevska
authors.affiliation: Technical University of Ilmenau, Ilmenau 98693, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Ritter
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D037741:Fullerenes / Q000494:pharmacology*; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017319:Photosensitizing Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D037741:Fullerenes; D017319:Photosensitizing Agents; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases; C069837:fullerene C60