title: The attenuation of early benzo(a)pyrene-induced carcinogenic insults by diallyl disulfide (DADS) in MCF-10A cells.
abstract: Diallyl disulfide (DADS), a garlic organosulfur compound, has been researched as a cancer prevention agent; however, the role of DADS in the suppression of cancer initiation in nonneoplastic cells has not been elucidated. To evaluate DADS inhibition of early carcinogenic events, MCF-10A cells were pretreated (PreTx) with DADS followed by the ubiquitous carcinogen benzo(a)pyrene (BaP), or cotreated (CoTx) with DADS and BaP for up to 24 h. The cells were evaluated for changes in cell viability/proliferation, cell cycle, induction of peroxide formation, and DNA damage. BaP induced a statistically significant increase in cell proliferation at 6 h, which was attenuated with DADS CoTx. PreTx with 6 and 60 μM of DADS inhibited BaP-induced G2/M arrest by 68% and 78%, respectively. DADS, regardless of concentration or method, inhibited BaP-induced extracellular aqueous peroxide formation within 24 h. DADS attenuated BaP-induced DNA single-strand breaks at all time points through both DADS Pre- and CoTx, with significant inhibition for all treatments sustained after 6 h. DADS was effective in inhibiting BaP-induced cell proliferation, cell cycle transitions, reactive oxygen species, and DNA damage in a normal cell line, and thus may inhibit environmentally induced breast cancer initiation.
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida Agricultural and Mechanical University, Tallahassee, Florida 32307, USA.
authors.forename: Yasmeen M
authors.initials: YM
authors.lastname: Nkrumah-Elie
authors.forename: Jayne S
authors.initials: JS
authors.lastname: Reuben
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Hudson
authors.forename: Equar
authors.initials: E
authors.lastname: Taka
authors.forename: Ramesh
authors.initials: R
authors.lastname: Badisa
authors.forename: Tiffany
authors.initials: T
authors.lastname: Ardley
authors.forename: Bridg'ette
authors.initials: B
authors.lastname: Israel
authors.forename: Sakeenah Y
authors.initials: SY
authors.lastname: Sadrud-Din
authors.forename: Ebenezer T
authors.initials: ET
authors.lastname: Oriaku
authors.forename: Selina F
authors.initials: SF
authors.lastname: Darling-Reed
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018890:Chemoprevention; D004249:DNA Damage / Q000187:drug effects; D004220:Disulfides / Q000494:pharmacology*; D005737:Garlic / Q000737:chemistry; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000498:Allyl Compounds; D002273:Carcinogens; D004220:Disulfides; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D001564:Benzo(a)pyrene; C028009:diallyl disulfide