Resveratrol is an effective inducer of CArG-driven TNF-alpha gene therapy

Cancer Gene Ther. 2008 Mar;15(3):133-9. doi: 10.1038/sj.cgt.7701103. Epub 2007 Dec 21.


We report the anticarcinogenic, anti-aging polyphenol resveratrol activates the radio- and chemo-inducible cancer gene therapy vector Ad.Egr.TNF, a replication-deficient adenovirus that expresses human tumor necrosis factor alpha (TNF-alpha) under control of the Egr-1 promoter. Like ionizing radiation or chemotherapeutic agents previously shown to activate Ad.Egr.TNF, resveratrol also induces Egr-1 expression from its chromosomal locus with a possible role for Egr-1 promoter CC(A+T)richGG sequences in the expression of TNF-alpha. Resveratrol induction of TNF-alpha in Ad.Egr.TNF-infected tumor xenografts demonstrated antitumor response in human and rat tumor models comparable to that of radio- or chemotherapy-induced TNF-alpha. Although sirtuins are known targets of resveratrol, in vitro inhibition of SIRT1 activity did not abrogate resveratrol induction of Egr-1 expression. This suggests that SIRT1 is not essential to mediate resveratrol induction of Egr-1. Nevertheless, control of transgene expression via resveratrol activation of Egr-1 may extend use of Ad.Egr.TNF to patients intolerant of radiation or cytotoxic therapy and offer a novel tool for development of other inducible gene therapies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation / drug effects
  • Adenoviridae / genetics*
  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Etoposide / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genetic Therapy / methods*
  • Humans
  • Mice
  • Mice, Nude
  • Rats
  • Resveratrol
  • Sirtuins / metabolism
  • Stilbenes / pharmacology*
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Xenograft Model Antitumor Assays / methods*


  • Early Growth Response Protein 1
  • Stilbenes
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53
  • Etoposide
  • Sirtuins
  • Resveratrol