A manganese porphyrin superoxide dismutase mimetic enhances tumor radioresponsiveness.
OBJECTIVE
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
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.
Moeller
Benjamin J
BJ
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Batinic-Haberle
Ines
I
Spasojevic
Ivan
I
Rabbani
Zahid N
ZN
Anscher
Mitchell S
MS
Vujaskovic
Zeljko
Z
Dewhirst
Mark W
MW
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D017077:Culture Media, Conditioned; D004354:Drug Screening Assays, Antitumor; D005260:Female; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000098:blood supply / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012377:Rodentia
D017077:Culture Media, Conditioned; D008665:Metalloporphyrins; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; C431023:manganese (III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin