title: Bioactive food components prevent carcinogenic stress via Nrf2 activation in BRCA1 deficient breast epithelial cells.
abstract: Although BRCA1 is the most prevalent genetic factor in breast cancer, the pathologic mechanism of tumorigenesis caused by its deficiency has not been elucidated. We have previously demonstrated that BRCA1 can modulate responses to xenobiotic stress by regulating expression of genes involved in metabolic activation, detoxification and antioxidant reactions. In this study, we examined whether BRCA1 deficiency is more vulnerable to xenobiotic stress by employing an in vitro cell model system. Benzo[a]pyrene (B[a]P), used as a xenobiotic insult, increased intracellular reactive oxygen species (ROS) levels in breast epithelial cells. Accumulation of ROS upon B[a]P exposure was significantly augmented by abrogation of BRCA1 compared to the control. Overexpression of Nrf2 in BRCA1 deficient cells reduced elevated ROS to the control levels. Bioactive food components such as sulforaphane (SFN) and resveratrol (RSV) significantly reduced B[a]P-induced ROS accumulation regardless of BRCA1 presence. In addition, these bioactive food components increased Nrf2 levels and Nrf2 transcriptional activity, which led to attenuation of B[a]P-induced DNA damages. Likewise, incubation with bioactive food components reduced B[a]P-mediated DNA damage in BRCA1 deficient cells. In conclusion, we demonstrated that the lack of BRCA1 renders cells more susceptible to ROS-induced DNA damage, which may eventually result in tumorigenesis, and that administration of Nrf2-activating bioactive food components can reduce those risks.
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW, Washington, DC 20057, USA.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Kang
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Hong
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Antai
authors.initials: A
authors.lastname: Wang
authors.forename: Insoo
authors.initials: I
authors.lastname: Bae
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology; D019313:BRCA1 Protein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000633:toxicity; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D019313:BRCA1 Protein; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013454:Sulfoxides; D013861:Thiocyanates; D001564:Benzo(a)pyrene; C016766:sulforaphane