Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 53, Issue 12, Pages 1573-1581Publisher
WILEY
DOI: 10.1002/mnfr.200900011
Keywords
Anticancer actions; Apoptosis; Cell proliferation; Human breast cancer; Vitamin E
Categories
Funding
- Public Health Service [CA59739]
- Clayton Foundation for Research
- American Institute for Cancer Research [0513115]
- National Institute of Environmental Health Sciences [ES007784]
- NATIONAL CANCER INSTITUTE [R01CA059739] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P30ES007784] Funding Source: NIH RePORTER
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Two naturally occurring dietary sources of vitamin E (i.e. RRR-alpha-tocopherol (alpha T) and RRR-gamma-tocopherol (gamma T)), the manufactured synthetic form of vitamin E, all-racemic-alpha-tocopherol (all-rac-alpha T), as well as a potent antitumor analog of vitamin E, RRR-alpha-tocopherol ether-linked acetic acid analog (alpha-TEA), were assessed for anticancer actions. Data showed that gamma T, all-rac-alpha T, and alpha-TEA but not alpha T or alpha T+gamma T significantly inhibited tumor burden of human MDA-MB-231 cells in nude mice. Immunohistochemical analyses of tumor tissue showed that all-rac-alpha T and alpha-TEA increased apoptosis and decreased proliferation in tumor cells while gamma T was associated with increased tumor cell apoptosis only. In vitro data showed alpha-TEA and gamma T but not all-rac-alpha T or alpha T to inhibit colony formation and induce apoptosis. Anticancer actions of alpha-TEA and gamma T involved death receptor 5 protein upregulation, Survivin protein downregulation and poly (ADP-ribose) polymerase cleavage, all of which were blocked by co-treatment with alpha T. In summary, both gamma T and alpha-TEA exhibited promising anticancer properties in vivo and in vitro, whereas all-rac-alpha T exhibited promising anticancer properties in vivo only. Importantly, alpha T not only failed to exhibit anticancer properties but it also reduced anticancer actions of gamma T in vivo and gamma T and alpha-TEA in vitro.
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