Comparison of the effects of the chemopreventive agent resveratrol and its synthetic analog trans 3,4,5,4'-tetramethoxystilbene (DMU-212) on adenoma development in the Apc(Min+) mouse and cyclooxygenase-2 in human-derived colon cancer cells

Int J Cancer. 2005 Jun 10;115(2):194-201. doi: 10.1002/ijc.20884.


Naturally occurring molecules with putative cancer chemopreventive properties such as the phytoalexin resveratrol (3,5,4'-trihydroxystilbene) are lead molecules that guide the design of novel agents with improved pharmacologic properties. The synthetic resveratrol analog 3,4,5,4'-tetramethoxystilbene (DMU-212) has been shown to possess stronger antiproliferative properties in human colon cancer cells than resveratrol. We tested the hypothesis that DMU-212 is also a more potent inhibitor of adenoma development in the Apc(Min+) mouse, a model of human intestinal carcinogenesis. Apc(Min+) mice received either stilbene derivative with the diet (0.2%), and adenomas were counted after experiments were terminated. Resveratrol and DMU-212 decreased adenoma load by 27% and 24%, respectively, compared to untreated controls. Cyclooxygenase (COX) enzymes are important mechanistic targets of resveratrol, and we investigated whether DMU-212 interferes with the expression and activity of COX in human colon cells. Incubation of HCA-7 cancer cells for 24-96 hr with either stilbene derivative (1-50 microM) decreased prostaglandin E-2 (PGE-2) production, but only resveratrol decreased COX-2 protein expression. In mice, which received either stilbene derivative (0.2%) for 3 weeks with their diet, PGE-2 levels in the intestinal mucosa were reduced by between 45% and 62% compared to mice on control diet. While resveratrol inhibited enzyme activity in purified COX preparations, DMU-212 failed to do so. The PGE-2 decrease seen with DMU-212 in cells and in vivo is probably mediated via its metabolites. The results suggest that alteration of the resveratrol molecule to generate DMU-212 does not abrogate its ability to decrease adenoma number in Apc(Min+) mice or to interfere with PGE-2 generation in cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / enzymology
  • Adenoma / pathology
  • Adenoma / prevention & control*
  • Animals
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Chemoprevention
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control*
  • Cyclooxygenase 2
  • Diet
  • Dinoprostone / metabolism
  • Female
  • Genes, APC / physiology
  • Intestinal Mucosa / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Resveratrol
  • Ribonucleotide Reductases / antagonists & inhibitors
  • Stilbenes / therapeutic use*
  • Tissue Distribution


  • 3,4,5,4'-tetramethoxystilbene
  • Antineoplastic Agents, Phytogenic
  • Stilbenes
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Ribonucleotide Reductases
  • Dinoprostone
  • Resveratrol