Sulforaphane inhibits 4-aminobiphenyl-induced DNA damage in bladder cells and tissues.
Sulforaphane (SF) is a well-known chemopreventive phytochemical and occurs in broccoli and to a lesser extent in other cruciferous vegetables, whereas 4-aminobiphenyl (ABP) is a major human bladder carcinogen and is present at significant levels in tobacco smoke. Here, we show that SF inhibits ABP-induced DNA damage in both human bladder cells in vitro and mouse bladder tissue in vivo, using dG-C8-ABP as a biomarker, which is the predominant ABP-DNA adduct formed in human bladder cells and tissues. SF activates NF-E2 related factor-2 (Nrf2), which is a well-recognized chemopreventive target and activates the Nrf2-regulated cytoprotective signaling pathway. Comparison between wild-type mice and mice without Nrf2 shows that Nrf2 activation is required by SF for inhibition of ABP-induced DNA damage. Moreover, Nrf2 activation by SF in the bladder occurs primarily in the epithelium, which is the principal site of bladder cancer development. These data, together with our recent observation that SF-enriched broccoli sprout extracts strongly inhibits N-butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder cancer development, suggest that SF is a highly promising agent for bladder cancer prevention and provides a mechanistic insight into the repeated epidemiological observation that consumption of broccoli is inversely associated with bladder cancer risk and mortality.
Ding
Yi
Y
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Paonessa
Joseph D
JD
Randall
Kristen L
KL
Argoti
Dayana
D
Chen
Lihua
L
Vouros
Paul
P
Zhang
Yuesheng
Y
D000611:Aminobiphenyl Compounds / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D018736:DNA Adducts; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D017879:Isothiocyanates; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000502:physiology; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*
D000611:Aminobiphenyl Compounds; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D018736:DNA Adducts; D004273:DNA, Neoplasm; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D013454:Sulfoxides; D013861:Thiocyanates; C006757:4-biphenylamine; C016766:sulforaphane
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