Format

Send to

Choose Destination
Int J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):545-52.

A manganese porphyrin superoxide dismutase mimetic enhances tumor radioresponsiveness.

Author information

1
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.

Abstract

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.

PMID:
16168847
DOI:
10.1016/j.ijrobp.2005.05.026
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center