Overexpression of the human inducible nitric oxide synthase gene enhances radiation-induced apoptosis in colorectal cancer cells via a caspase-dependent mechanism

Peter Chung, Tracy Cook, Kaihong Liu, Yoram Vodovotz, Ruben Zamora, Sydney Finkelstein, Timothy Billiar, David Blumberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Nitric oxide (NO) has been reported to sensitize cancer cells to radiation. Since delivery of NO to tumors is limited in vivo by systemic toxicity of NO, we examined the potential of gene delivery of the human inducible nitric oxide synthase (iNOS) gene as a means of achieving high output NO production. We successfully transduced two colorectal cancer cell lines as evidenced by increased iNOS protein accumulation and nitrite production. We found that overexpression of iNOS enhanced the effects of radiation on apoptosis in both cell lines in a caspase-dependent fashion. Gene transfer of iNOS holds much promise as a potential radiosensitizer of cancer cells since it increases apoptosis in an additive manner with radiation.

Original languageEnglish
Pages (from-to)119-126
Number of pages8
JournalNitric Oxide - Biology and Chemistry
Volume8
Issue number2
DOIs
StatePublished - Mar 2003
Externally publishedYes

Keywords

  • Cancer
  • Gene therapy
  • Inducible nitric oxide synthase (iNOS)
  • Nitric oxide
  • Radiation

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