title: Dietary administration of δ- and γ-tocopherol inhibits tumorigenesis in the animal model of estrogen receptor-positive, but not HER-2 breast cancer.
abstract: Tocopherol, a member of the vitamin E family, consists of four forms designated as α, β, γ, and δ. Several large cancer prevention studies with α-tocopherol have reported no beneficial results, but recent laboratory studies have suggested that δ- and γ-tocopherol may be more effective. In two different animal models of breast cancer, the chemopreventive activities of individual tocopherols were assessed using diets containing 0.3% of tocopherol (α-, δ-, or γ-) or 0.3% of a γ-tocopherol rich mixture (γ-TmT). Although administration of tocopherols did not prevent human epidermal growth factor receptor 2 (HER2/neu)-driven tumorigenesis, δ- and γ-tocopherols inhibited hormone-dependent mammary tumorigenesis in N-methyl-N-nitrosourea (NMU)-treated female Sprague-Dawley rats. NMU-treated rats showed an average tumor burden of 10.6 ± 0.8 g in the control group at 11 weeks, whereas dietary administration of δ- and γ-tocopherols significantly decreased tumor burden to 7.2 ± 0.8 g (P < 0.01) and 7.1 ± 0.7 g (P < 0.01), respectively. Tumor multiplicity was also reduced in δ- and γ-tocopherol treatment groups by 42% (P < 0.001) and 32% (P < 0.01), respectively. In contrast, α-tocopherol did not decrease tumor burden or multiplicity. In mammary tumors, the protein levels of proapoptotic markers (BAX, cleaved caspase-9, cleaved caspase-3, cleaved PARP) were increased, whereas antiapoptotic markers (Bcl-2, XIAP) were inhibited by δ-tocopherol, γ-tocopherol, and γ-TmT. Furthermore, markers of cell proliferation (PCNA, PKCα), survival (PPAR-γ, PTEN, phospho-Akt), and cell cycle (p53, p21) were affected by δ- and γ-tocopherols. Both δ- and γ-tocopherols, but not α-tocopherol, seem to be promising agents for the prevention of hormone-dependent breast cancer.
authors.affiliation: Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Smolarek
authors.forename: Jae Young
authors.initials: JY
authors.lastname: So
authors.forename: Brenda
authors.initials: B
authors.lastname: Burgess
authors.forename: Ah-Ng Tony
authors.initials: AN
authors.lastname: Kong
authors.forename: Kenneth
authors.initials: K
authors.lastname: Reuhl
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Weichung Joe
authors.initials: WJ
authors.lastname: Shih
authors.forename: Guangxun
authors.initials: G
authors.lastname: Li
authors.forename: Mao-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Yu-Kuo
authors.initials: YK
authors.lastname: Chen
authors.forename: Chung S
authors.initials: CS
authors.lastname: Yang
authors.forename: Nanjoo
authors.initials: N
authors.lastname: Suh
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000178:diet therapy / Q000235:genetics / Q000473:pathology; D002277:Carcinoma / Q000178:diet therapy* / Q000235:genetics / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000178:diet therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D017207:Rats, Sprague-Dawley; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D024505:Tocopherols / Q000008:administration & dosage* / Q000494:pharmacology; D024504:gamma-Tocopherol / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D024505:Tocopherols; D024504:gamma-Tocopherol; C479072:delta-tocopherol