Modulation of reactive oxygen species in pancreatic cancer

Melissa L.T. Teoh, Wenqing Sun, Brian J. Smith, Larry W. Oberley, Joseph J. Cullen

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Purpose: The aim of the present study was to compare the effects of the three different forms of the antioxidant enzyme superoxide dismutase [i.e., manganese superoxide dismutase (MnSOD), copper zinc superoxide dismutase (CuZnSOD), and extracellular superoxide dismutase (EcSOD)] on the malignant phenotype of human pancreatic cancer. Experimental Design: Human pancreatic cancer cell lines were infected with adenoviral vectors containing the cDNAs for three different forms of the antioxidant enzyme SOD. Intratumoral injections of the adenoviral vectors were used in nude mice with human tumor xenografts. Results: Increases in immunoreactive protein and enzymatic activity were seen after infections with the AdMnSOD, AdCuZnSOD, or AdEcSOD constructs. Increased SOD activity decreased superoxide levels and increased hydrogen peroxide levels. Increasing SOD levels correlated with increased doubling time. Cell growth and plating efficiency decreased with increasing amounts of the adenoviral constructs, with the AdCuZnSOD vector having the greatest effect in decreasing in vitro tumor growth. In contrast, inhibiting endogenous SOD with small interfering RNA increased superoxide levels and promoted tumor growth. Of the three SODs, tumors grew the slowest and survival was increased the greatest in nude mice injected with the AdEcSOD construct. Conclusions: Scavenging plasma membrane-generated superoxide may prove beneficial for suppression of pancreatic cancer growth.

Original languageEnglish (US)
Pages (from-to)7441-7450
Number of pages10
JournalClinical Cancer Research
Volume13
Issue number24
DOIs
StatePublished - Dec 15 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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