Tocopherols inhibit oxidative and nitrosative stress in estrogen-induced early mammary hyperplasia in ACI rats.
Oxidative stress is known to play a key role in estrogen-induced breast cancer. This study assessed the chemopreventive activity of the naturally occurring γ-tocopherol-rich mixture of tocopherols (γ-TmT) in early stages of estrogen-induced mammary hyperplasia in ACI rats. ACI rats provide an established model of rodent mammary carcinogenesis due to their high sensitivity to estrogen. Female rats were implanted with 9 mg of 17β-estradiol (E2) in silastic tubings and fed with control or 0.3% γ-TmT diet for 1, 3, 7, and 14 d. γ-TmT increased the levels of tocopherols and their metabolites in the serum and mammary glands of the rats. Histological analysis revealed mammary hyperplasia in the E2 treated rats fed with control or γ-TmT diet. γ-TmT decreased the levels of E2-induced nitrosative and oxidative stress markers, nitrotyrosine, and 8-oxo-dG, respectively, in the hyperplastic mammary tissues. 8-Isoprostane, a marker of oxidative stress in the serum, was also reduced by γ-TmT. Noticeably, γ-TmT stimulated Nrf2-dependent antioxidant response in the mammary glands of E2 treated rats, evident from the induced mRNA levels of Nrf2 and its downstream antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase. Therefore, inhibition of nitrosative/oxidative stress through induction of antioxidant response is the primary effect of γ-TmT in early stages of E2-induced mammary hyperplasia. Due to its cytoprotective activity, γ-TmT could be a potential natural agent for the chemoprevention of estrogen-induced breast cancer.
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Soumyasri
S
Das Gupta
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Jae Young
JY
So
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Brian
B
Wall
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Joseph
J
Wahler
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Amanda K
AK
Smolarek
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Sudathip
S
Sae-Tan
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Kelvin Y
KY
Soewono
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Haixiang
H
Yu
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Mao-Jung
MJ
Lee
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
Paul E
PE
Thomas
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.|Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
Chung S
CS
Yang
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.|Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
Nanjoo
N
Suh
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001941:Breast Diseases / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D019587:Dietary Supplements / Q000032:analysis; D004967:Estrogens; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology*; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011912:Rats, Inbred ACI; D024505:Tocopherols / Q000627:therapeutic use*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D015854:Up-Regulation
D000975:Antioxidants; D004967:Estrogens; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D012333:RNA, Messenger; C002744:3-nitrotyrosine; D014443:Tyrosine; D024505:Tocopherols
breast cancer; estrogen; oxidative stress; vitamin E