Diallyl sulfide inhibits PhIP-induced cell death via the inhibition of DNA strand breaks in normal human breast epithelial cells.
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.
Aboyade-Cole
Ayoola
A
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
Darling-Reed
Selina
S
Oriaku
Ebenezer
E
McCaskill
Michael
M
Thomas
Ronald
R
D000498:Allyl Compounds / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001940:Breast / Q000187:drug effects* / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D020552:Comet Assay; D065607:Cytochrome P-450 Enzyme Inhibitors; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D013440:Sulfides / Q000494:pharmacology*
D000498:Allyl Compounds; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D013440:Sulfides; C038491:allyl sulfide; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine