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: Amanda K Smolarek, Jae Young So, Brenda Burgess, Ah-Ng Tony Kong, Kenneth Reuhl, Yong Lin, Weichung Joe Shih, Guangxun Li, Mao-Jung Lee, Yu-Kuo Chen, Chung S Yang, Nanjoo Suh
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 5 Issue 11 Pg. 1310-20 (Nov 2012) ISSN: 1940-6215 [Electronic] United States
• PMID: 22964476 (Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Estrogen
• gamma-Tocopherol
• Receptor, ErbB-2
• delta-tocopherol
• Tocopherols

Topics

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