HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Effects of 5,6-benzoflavone, indole-3-carbinol (I3C) and diindolylmethane (DIM) on chemically-induced mammary carcinogenesis: is DIM a substitute for I3C?

Abstract
The abilities of 5,6-benzoflavone (5,6-BF, a synthetic flavonoid), indole-3-carbinol (I3C, a plant derived product) or diindolylmethane (DIM, a condensation product of I3C) to alter the induction of mammary cancers induced by the carcinogens 7,12-dimethylbenzanthracene (DMBA) or N-methyl-N-nitrosourea (MNU) were evaluated. Interestingly, the first two agents act as aryl hydrocarbon receptor (AhR) agonists, while DIM does not. The agents were initially examined for their ability to inhibit DMBA-induced mammary carcinogenesis. Agents were administered for 14 days starting 7 days prior to a single dose of the carcinogen. Evaluated over an extensive range of doses (165, 550 and 1650 ppm in the diet), 5,6-BF caused a dose-dependent decrease of mammary cancers. In addition, 5,6-BF at doses of 1650 and 165 ppm in the diet blocked the induction of DMBA-induced DNA adducts in the mammary gland by approximately 85% and 45%, respectively. In contrast, DIM (180 or 20 mg/kg BW/day) failed to block induction of DMBA tumors. The effect of these agents on the promotion/progression phase of carcinogenesis using the MNU mammary cancer model was also determined. 5,6-BF (1650 or 165 ppm in the diet), I3C (180 or 60 mg/kg BW/day administered by gavage), or DIM (180 or 60 mg/kg BW/day by gavage) were initiated 5 days after the administration of MNU, and continually thereafter. 5,6-BF decreased MNU- induced mammary tumor multiplicity by 40-60%. I3C reduced tumor multiplicity at the high dose, while DIM at either dose had minimal effects on tumor multiplicity. Thus, 5,6-BF and I3C were highly effective against initiation of DMBA-induced mammary carcinogenesis, and were also effective against MNU-induced tumors during the promotion/progression phase of carcinogenesis. In contrast, DIM had minimal effects in either model; arguing that administration of DIM is not analogous to administration of I3C.
AuthorsRonald A Lubet, Brandy M Heckman, Silvio L De Flora, Vernon E Steele, James A Crowell, M Margaret Juliana, Clinton J Grubbs
JournalOncology reports (Oncol Rep) Vol. 26 Issue 3 Pg. 731-6 (Sep 2011) ISSN: 1791-2431 [Electronic] Greece
PMID21617870 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Anticarcinogenic Agents
  • Indoles
  • 9,10-Dimethyl-1,2-benzanthracene
  • beta-Naphthoflavone
  • Methylnitrosourea
  • indole-3-carbinol
  • Aryl Hydrocarbon Hydroxylases
  • Cyp1b1 protein, rat
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1B1
  • 3,3'-diindolylmethane
Topics
  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Anticarcinogenic Agents (pharmacology)
  • Aryl Hydrocarbon Hydroxylases (genetics, metabolism)
  • Cytochrome P-450 CYP1A1 (genetics, metabolism)
  • Cytochrome P-450 CYP1B1
  • Epithelial Cells (drug effects, pathology)
  • Female
  • Indoles (pharmacology)
  • Mammary Glands, Animal (drug effects, pathology)
  • Mammary Neoplasms, Experimental (chemically induced, pathology, prevention & control)
  • Methylnitrosourea
  • Rats
  • Rats, Sprague-Dawley
  • Transcription, Genetic
  • Tumor Burden
  • beta-Naphthoflavone (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: