Dietary Administration of δ- and γ-Tocopherol Inhibits Tumorigenesis in the Animal Model of Estrogen Receptor–Positive, but not HER-2 Breast Cancer
- 1 November 2012
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Prevention Research
- Vol. 5 (11), 1310-1320
- https://doi.org/10.1158/1940-6207.capr-12-0263
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. Cancer Prev Res; 5(11); 1310–20. ©2012 AACR.Keywords
This publication has 38 references indexed in Scilit:
- Oxidative Stress, Tumor Microenvironment, and Metabolic Reprogramming: A Diabolic LiaisonInternational Journal of Cell Biology, 2012
- Chemopreventive Activity of Vitamin E in Breast Cancer: A Focus on γ- and δ-TocopherolNutrients, 2011
- δ-Tocopherol Is More Active than α- or γ-Tocopherol in Inhibiting Lung Tumorigenesis In VivoCancer Prevention Research, 2011
- Gemini vitamin D analog suppresses ErbB2-positive mammary tumor growth via inhibition of ErbB2/AKT/ERK signalingThe Journal of Steroid Biochemistry and Molecular Biology, 2010
- Lifestyle as risk factor for cancer: Evidence from human studiesCancer Letters, 2010
- Analysis of Multiple Metabolites of Tocopherols and Tocotrienols in Mice and HumansJournal of Agricultural and Food Chemistry, 2010
- Mixed Tocopherols Prevent Mammary Tumorigenesis by Inhibiting Estrogen Action and Activating PPAR-γClinical Cancer Research, 2009
- Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other CancersJAMA, 2009
- Cancer chemoprevention with dietary phytochemicalsNature Reviews Cancer, 2003
- Vitamin E as an in Vitro and in Vivo AntioxidantaAnnals of the New York Academy of Sciences, 1989