title: A manganese porphyrin superoxide dismutase mimetic enhances tumor radioresponsiveness.
abstract: OBJECTIVE
  To determine the effect of the superoxide dismutase mimetic Mn(III) tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)) on tumor radioresponsiveness.
  
  
  METHODS
  Various rodent tumor (4T1, R3230, B16) and endothelial (SVEC) cell lines were exposed to MnTE-2-PyP(5+) and assayed for viability and radiosensitivity in vitro. Next, tumors were treated with radiation and MnTE-2-PyP(5+)in vivo, and the effects on tumor growth and vascularity were monitored.
  
  
  RESULTS
  In vitro, MnTE-2-PyP(5+) was not significantly cytotoxic. However, at concentrations as low as 2 mumol/L it caused 100% inhibition of secretion by tumor cells of cytokines protective of irradiated endothelial cells. In vivo, combined treatment with radiation and MnTE-2-PyP(5+) achieved synergistic tumor devascularization, reducing vascular density by 78.7% within 72 h of radiotherapy (p < 0.05 vs. radiation or drug alone). Co-treatment of tumors also resulted in synergistic antitumor effects, extending tumor growth delay by 9 days (p < 0.01).
  
  
  CONCLUSIONS
  These studies support the conclusion that MnTE-2-PyP(5+), which has been shown to protect normal tissues from radiation injury, can also improve tumor control through augmenting radiation-induced damage to the tumor vasculature.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Moeller
authors.forename: Ines
authors.initials: I
authors.lastname: Batinic-Haberle
authors.forename: Ivan
authors.initials: I
authors.lastname: Spasojevic
authors.forename: Zahid N
authors.initials: ZN
authors.lastname: Rabbani
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Anscher
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Vujaskovic
authors.forename: Mark W
authors.initials: MW
authors.lastname: Dewhirst
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D017077:Culture Media, Conditioned; D004354:Drug Screening Assays, Antitumor; D005260:Female; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000098:blood supply / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012377:Rodentia
chemical_list: D017077:Culture Media, Conditioned; D008665:Metalloporphyrins; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; C431023:manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin