A manganese porphyrin superoxide dismutase mimetic enhances tumor radioresponsiveness.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Moeller, BJ; Batinic-Haberle, I; Spasojevic, I; Rabbani, ZN; Anscher, MS; Vujaskovic, Z; Dewhirst, MW

Published Date

  • October 1, 2005

Published In

Volume / Issue

  • 63 / 2

Start / End Page

  • 545 - 552

PubMed ID

  • 16168847

Pubmed Central ID

  • 16168847

International Standard Serial Number (ISSN)

  • 0360-3016

Digital Object Identifier (DOI)

  • 10.1016/j.ijrobp.2005.05.026

Language

  • eng

Conference Location

  • United States