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Accession Number ADA564470
Title Modulation of Estrogen-Depurinating DNA Adducts by Sulforaphane for Breast Cancer.
Publication Date Oct 2012
Media Count 43p
Personal Author L. Yang
Abstract Sulforaphane (SFN), a bioavailable phytochemical found in young broccoli, is a potent inducer of detoxification enzymes such as NAD(P)H:quinone oxidoreductase (NQO1) and glutathione-S-transferase (GST) via the Kelch-like ECH-associated protein 1 (Keap1) - Nuclear Factor- E2-related factor (Nrf2) signaling pathway. To test the hypothesis that SFN may be an ideal chemoprevention agent to block estrogen-mediated carcinogenesis, we treated the ER-negative, nontumorigenic human breast epithelial MCF10A cell line with either vehicle or SFN (10 M) and E2 or 4-OHE2. Results show that NQO1 was up- regulated at the mRNA (approximately 2fold), protein (approximately 3fold) and activity levels (approximately 3fold) by SFN treatment. Estrogen metabolites and depurinating DNA adducts in the cell culture medium were partially purified by solid phase extraction and then analyzed by UHPLC- ESI-MS/MS. Following E2 treatment, the depurinated adducts 4- OHE(sub 1/2)-1-N3Ade and 4-OHE 1/2-1-N7Gua were significantly lower in SFN treated cells compared to vehicle (0.03 0.01 versus 0.07 0.02 pmole/106cell, p=0.0294); 4-OHE(sub 1/2)- glutathione conjugates were significantly higher following SFN treatment (1.54 0.37 versus 0.83 0.19 pmole/106cell, p=0.0015) as were 4-OCH3E(sub 1/2) (5.36 0.16 versus 1.81 0.20pmole/106cell).
Keywords Breast cancer
Cells(Biology)
Cultures(Biology)
Deoxyribonucleic acids
Estrogen depurinating dna adducts
Glutathione
Hypotheses
Metabolites
Oxidoreductases
Potency
Proteins
Quinones
Sulforaphane


 
Source Agency Non Paid ADAS
NTIS Subject Category 57B - Biochemistry
57E - Clinical Medicine
Corporate Author Pittsburgh Univ., PA.
Document Type Technical report
Title Note Annual summary rept. 15 Sep 2011-14 Sep 2012.
NTIS Issue Number 1303
Contract Number W81XWH-11-1-0731

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