δ- and γ-tocopherols, but not α-tocopherol, inhibit colon carcinogenesis in azoxymethane-treated F344 rats.

Abstract

The cancer preventive activity of vitamin E has been extensively discussed, but the activities of specific forms of tocopherols have not received sufficient attention. Herein, we compared the activities of δ-tocopherol (δ-T), γ-T, and α-T in a colon carcinogenesis model. Male F344 rats, seven weeks old, were given two weekly subcutaneous injections of azoxymethane (AOM) each at a dose of 15 mg/kg body weight. Starting 1 week before the AOM injection, the animals were maintained on a modified AIN76A diet, or the same diet containing 0.2% of δ-T, γ-T, α-T, or a γ-T-rich mixture of tocopherols (γ-TmT), until the termination of the experiment at 8 weeks after the second AOM injection. δ-T treatment showed the strongest inhibitory effect, decreasing the numbers of aberrant crypt foci by 62%. γ-T and γ-TmT were also effective, but α-T was not. Immunohistochemical analysis showed that δ-T and γ-T treatments reduced the levels of 4-hydroxynonenal and nitrotyrosine and the expression of cyclin D1 in the colon, preserved the expression of PPAR-γ, and decreased the serum levels of prostaglandin E2 and 8-isoprostane. Supplementation with 0.2% δ-T, γ-T, or α-T increased the respective levels of tocopherols and their side-chain degradation metabolites in the serum and colon tissues. Rather high concentrations of δ-T and γ-T and their metabolites were found in colon tissues. Our study provides the first evidence for the much higher cancer preventive activity of δ-T and γ-T than α-T in a chemically induced colon carcinogenesis model. It further suggests that δ-T is more effective than γ-T.

• Authors: Fei Guan, Guangxun Li, Anna B Liu, Mao-Jung Lee, Zhihong Yang, Yu-Kuo Chen, Yong Lin, Weichung Shih, Chung S Yang
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 5 Issue 4 Pg. 644-54 (Apr 2012) ISSN: 1940-6215 [Electronic] United States
• PMID: 22366914 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: 2012 AACR

Chemical References

• Aldehydes
• Anticarcinogenic Agents
• Cyclin D1
• 8-epi-prostaglandin F2alpha
• 3-nitrotyrosine
• Tyrosine
• gamma-Tocopherol
• Dinoprost
• alpha-Tocopherol
• delta-tocopherol
• 4-hydroxy-2-nonenal
• Dinoprostone
• Azoxymethane
• Tocopherols

Topics

• Aldehydes (pharmacology)
• Animals
• Anticarcinogenic Agents (pharmacology)
• Azoxymethane (pharmacology)
• Colonic Neoplasms (prevention & control)
• Cyclin D1 (biosynthesis)
• Dinoprost (analogs & derivatives, pharmacology)
• Dinoprostone (metabolism)
• Immunohistochemistry (methods)
• Male
• Models, Chemical
• Rats
• Rats, Inbred F344
• Tocopherols (metabolism)
• Tyrosine (analogs & derivatives, chemistry)
• alpha-Tocopherol (metabolism)
• gamma-Tocopherol (metabolism)