Diallyl sulfide inhibits PhIP-induced cell death via the inhibition of DNA strand breaks in normal human breast epithelial cells

Oncol Rep. 2008 Aug;20(2):319-23.

Abstract

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is associated with mammary carcinomas in animals and humans. PhIP is metabolized by CYP 1A1/1A2 and cytochrome b5 reductase, producing free radicals causing DNA strand breaks. Diallyl sulfide (DAS) prevents cancer in animals. We hypothesized that DAS will attenuate PhIP-induced DNA strand breaks and cell death. To test this hypothesis, we treated MCF-10A cells with PhIP, DAS and PhIP/DAS for 24, 48 and 72 h. DAS inhibited the PhIP-induced DNA strand breaks by 22% after 48 h and the strand breaks were completely inhibited at 72 h. PhIP reduced cell viability at each time point. However, DAS only attenuated this reduction in cell viability by 56% at 72 h. N-OH PhIP inhibited cell viability by 26% at 72 h. DAS completely attenuated this reduction in cell viability and may prevent PhIP-induced breast cancer via alterations in DNA damage and cell viability.

Publication types

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

MeSH terms

  • Allyl Compounds / pharmacology*
  • Anticarcinogenic Agents / pharmacology*
  • Breast / drug effects*
  • Breast / metabolism
  • Carcinogens / pharmacology
  • Cell Survival / drug effects*
  • Cells, Cultured
  • Comet Assay
  • Cytochrome P-450 Enzyme Inhibitors
  • DNA Breaks, Double-Stranded / drug effects*
  • Female
  • Humans
  • Imidazoles / pharmacology
  • Sulfides / pharmacology*

Substances

  • Allyl Compounds
  • Anticarcinogenic Agents
  • Carcinogens
  • Cytochrome P-450 Enzyme Inhibitors
  • Imidazoles
  • Sulfides
  • allyl sulfide
  • 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine