A manganese porphyrin superoxide dismutase mimetic enhances tumor radioresponsiveness

Int J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):545-52. doi: 10.1016/j.ijrobp.2005.05.026.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Vessels / drug effects
  • Blood Vessels / radiation effects
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / radiation effects
  • Culture Media, Conditioned
  • Drug Screening Assays, Antitumor
  • Female
  • Metalloporphyrins / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / blood supply
  • Neoplasms / radiotherapy*
  • Radiation Tolerance / drug effects*
  • Radiation-Protective Agents / pharmacology
  • Radiation-Sensitizing Agents / pharmacology*
  • Rats
  • Rats, Inbred F344
  • Rodentia


  • Culture Media, Conditioned
  • Metalloporphyrins
  • Radiation-Protective Agents
  • Radiation-Sensitizing Agents
  • manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin