Cancer chemoprevention drug development strategies for resveratrol

Vernon E. Steele, Michael J. Wargovich, Kathy McKee, Sheela Sharma, Betty P. Wilkinson, Gail P. Wyatt, Pu Gao, Gary J. Kelloff

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Cancer chemoprevention refers to the reduction of cancer incidence by administration of agents or drugs which inhibit, reverse, or retard the cancer process. Resveratrol has demonstrated a wide variety of biological activities which make it a good candidate for a chemopreventive agent. Many agents, such as resveratrol are currently being tested with the goal of developing safe and effective chemopreventive drugs for human use. Resveratrol was investigated as a potential chemopreventive agent using two in vitro assays to determine preliminary efficacy. In the first assay anchorage-independent growth was inhibited in the human lung tumor cells. In the second assay B[a]P-induced transformation was inhibited in primary rat tracheal epithelial cells. With these two positive in vitro results and a mechanistic hypothesis of action, animal testing was begun. The azoxymethane-induced aberrant colon crypt model is typically the next step in developmental strategy. Resveratrol was tested for its ability to inhibit aberrant colon crypts in the colon of F344 rats which had been treated with azoxymethane. One test protocol showed significant inhibition of aberrant colon crypts in a carcinogen treated rat model. Further development of this agent includes demonstration of the preventive efficacy in an in vivo tumorigenesis model, followed by preclinical pharmacology and toxicology testing. Phase I, II, and III clinical chemoprevention trials would be then performed to determine pharmacokinetics, safe dose levels, and chemopreventive effectiveness for New Drug Approval by the FDA.

Original languageEnglish (US)
Pages (from-to)62-68
Number of pages7
JournalPharmaceutical Biology
Volume36
Issue numberSUPPL.
DOIs
StatePublished - Dec 1 1998
Externally publishedYes

Keywords

  • Aberrant colon crypts
  • Chemoprevention
  • Colon cancer
  • Grape extracts
  • Prevention
  • Rat tracheal epithelial cells
  • Resveratrol

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine

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