A manganese porphyrin superoxide dismutase mimetic enhances tumor radioresponsiveness

Purpose: To determine the effect of the superoxide dismutase mimetic Mn(III) tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP5+) on tumor radioresponsiveness. Methods and Materials: Various rodent tumor (4T1, R3230, B16) and endothelial (SVEC) cell lines were exposed to MnTE-2-PyP5+ and assayed for viability and radiosensitivity in vitro. Next, tumors were treated with radiation and MnTE-2-PyP5+ in vivo, and the effects on tumor growth and vascularity were monitored. Results: In vitro, MnTE-2-PyP5+ was not significantly cytotoxic. However, at concentrations as low as 2 μmol/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-PyP5+ 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-PyP5+, 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. [Copyright &y& Elsevier]