title: Pharmacological effect of aminoferrocene in mice with L1210 leukemia.
abstract: OBJECTIVE
  To study the cytostatic and some biological effects of aminoferrocene using mice with L1210 lymphoid leukemia.
  
  
  METHODS
  Experiments were performed on BDF1 male mice (DBA/2, female × C57Bl/6, male) with transplantable L1210 lymphoid leukemia. Determination of antitumor activity of Benzyl-Fc Boron (Bn), it was injected intraperitoneally 6 times daily, starting on day 2 after L1210 leukemia cell transplantation. Doses of Bn such as 26; 260 and 2600 μg/kg were used. The determination of intracellular content of cardiolipin, thiols, reactive oxygen species (ROS) and also analysis of Annexin V positivity and mitochondrial transmembrane potential (JC-1 staining) were performed with use of flow cytometry. The levels of "free iron" complexes, transferrin active forms and the rate of NO generation were measured by EPR-specroscopy.
  
  
  RESULTS
  Six daily injections of Bn at a dose of 26 μg/kg resulted in an increased survival of mice with L1210 leukemia by 28% (p < 0.05). Bn led to an increase of apoptotic cells number and ROS amount in leukemia cells. Besides, Bn caused a decrease of cardiolipin and nonprotein thiol compounds content. The membrane electrochemical potential of cell mitochondria was decreased also after Bn administration. Studies using EPR-spectroscopy revealed a significant increase in a level of "free iron", content of transferrin active species and generation rate of NO by inducible NO-synthase in L1210 cells after aminoferrocene administration.
  
  
  CONCLUSIONS
  Our data indicate that Benzyl-Fc Boron can be promising candidate for realizing a new strategy of anticancer therapy with the use of ROS-inducing agents.
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: V F
authors.initials: VF
authors.lastname: Chekhun
authors.affiliation: Friedrich-Alexander University of Erlangen-Nürnberg, Department of Chemistry and Pharmacy, Organic Chemistry II, Henkestr. 42, Erlangen 91054, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Mokhir
authors.affiliation: Friedrich-Alexander University of Erlangen-Nürnberg, Department of Chemistry and Pharmacy, Organic Chemistry II, Henkestr. 42, Erlangen 91054, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Daum
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: I N
authors.initials: IN
authors.lastname: Todor
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: N Yu
authors.initials: NY
authors.lastname: Lukianova
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: Yu V
authors.initials: YV
authors.lastname: Shvets
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
authors.forename: A P
authors.initials: AP
authors.lastname: Burlaka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005296:Ferrous Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D005296:Ferrous Compounds; C000605505:N-ferrocenyl-N-benzylaminocarbonyloxymethyl-phenylboronic acid pinacol ester; D017382:Reactive Oxygen Species