PURPOSE: 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 AND MATERIALS: 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.
PURPOSE: 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 AND MATERIALS: 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: Ines Batinic-Haberle; Ivan Spasojevic; Hubert M Tse; Artak Tovmasyan; Zrinka Rajic; Daret K St Clair; Zeljko Vujaskovic; Mark W Dewhirst; Jon D Piganelli Journal: Amino Acids Date: 2010-05-16 Impact factor: 3.520
Authors: Kranti A Mapuskar; Carryn M Anderson; Douglas R Spitz; Ines Batinic-Haberle; Bryan G Allen; Rebecca E Oberley-Deegan Journal: Semin Radiat Oncol Date: 2019-01 Impact factor: 5.934
Authors: Tin Weitner; Ivan Kos; Huaxin Sheng; Artak Tovmasyan; Julio S Reboucas; Ping Fan; David S Warner; Zeljko Vujaskovic; Ines Batinic-Haberle; Ivan Spasojevic Journal: Free Radic Biol Med Date: 2013-01-15 Impact factor: 7.376
Authors: Ines Batinić-Haberle; Michael M Ndengele; Salvatore Cuzzocrea; Júlio S Rebouças; Ivan Spasojević; Daniela Salvemini Journal: Free Radic Biol Med Date: 2008-10-17 Impact factor: 7.376