Title: Dietary administration of δ- and γ-tocopherol inhibits tumorigenesis in the animal model of estrogen receptor-positive, but not HER-2 breast cancer.

Authors: Smolarek, Amanda K; So, Jae Young; Burgess, Brenda; Kong, Ah-Ng Tony; Reuhl, Kenneth; Lin, Yong; Shih, Weichung Joe; Li, Guangxun; Lee, Mao-Jung; Chen, Yu-Kuo; Yang, Chung S; Suh, Nanjoo

Published In Cancer Prev Res (Phila), (2012 Nov)

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.

PubMed ID: 22964476

MeSH Terms: Animals; Breast Neoplasms/diet therapy; Breast Neoplasms/genetics; Breast Neoplasms/pathology; Carcinoma/diet therapy*; Carcinoma/genetics; Carcinoma/pathology; Cell Transformation, Neoplastic/drug effects*; Dietary Supplements; Disease Models, Animal; Down-Regulation/drug effects; Female; Mammary Neoplasms, Experimental/diet therapy*; Mammary Neoplasms, Experimental/genetics; Mammary Neoplasms, Experimental/pathology; Mice; Mice, Transgenic; Rats; Rats, Sprague-Dawley; Receptor, ErbB-2/genetics; Receptor, ErbB-2/metabolism; Receptors, Estrogen/genetics*; Receptors, Estrogen/metabolism; Tocopherols/administration & dosage*; Tocopherols/pharmacology; gamma-Tocopherol/administration & dosage*; gamma-Tocopherol/pharmacology