Anticancer actions of natural and synthetic vitamin E forms: RRR-α-tocopherol blocks the anticancer actions of γ-tocopherol

• Published in: Molecular nutrition & food research 2009-12, Vol.53 (12), p.1573-1581
• Main Authors: Yu, Weiping, Jia, Li, Park, Sook-Kyung, Li, Jing, Gopalan, Archana, Simmons-Menchaca, Marla, Sanders, Bob G., Kline, Kimberly
• Format: Article
• Language: English
• Subjects: alpha-Tocopherol - blood; alpha-Tocopherol - chemistry; alpha-Tocopherol - pharmacology; Animals; Annexin A5 - metabolism; Anticancer actions; Antineoplastic Agents - antagonists & inhibitors; Antineoplastic Agents - blood; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Biomarkers; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Female; gamma-Tocopherol - antagonists & inhibitors; gamma-Tocopherol - blood; gamma-Tocopherol - pharmacology; Gene Expression Regulation, Neoplastic; Human breast cancer; Humans; Isomerism; Mice; Mice, Nude; Time Factors; Tocopherols - pharmacology; Tumor Burden - drug effects; Vitamin E; Xenograft Model Antitumor Assays
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.200900011

Two naturally occurring dietary sources of vitamin E (i.e. RRR‐α‐tocopherol (αT) and RRR‐γ‐tocopherol (γT)), the manufactured synthetic form of vitamin E, all‐racemic‐α‐tocopherol (all‐rac‐αT), as well as a potent antitumor analog of vitamin E, RRR‐α‐tocopherol ether‐linked acetic acid analog (α‐TEA), were assessed for anticancer actions. Data showed that γT, all‐rac‐αT, and α‐TEA but not αT or αT+γT significantly inhibited tumor burden of human MDA‐MB‐231 cells in nude mice. Immunohistochemical analyses of tumor tissue showed that all‐rac‐αT and α‐TEA increased apoptosis and decreased proliferation in tumor cells while γT was associated with increased tumor cell apoptosis only. In vitro data showed α‐TEA and γT but not all‐rac‐αT or αT to inhibit colony formation and induce apoptosis. Anticancer actions of α‐TEA and γT involved death receptor 5 protein upregulation, Survivin protein downregulation and poly (ADP‐ribose) polymerase cleavage, all of which were blocked by co‐treatment with αT. In summary, both γT and α‐TEA exhibited promising anticancer properties in vivo and in vitro, whereas all‐rac‐αT exhibited promising anticancer properties in vivo only. Importantly, αT not only failed to exhibit anticancer properties but it also reduced anticancer actions of γT in vivo and γT and α‐TEA in vitro.