title: Comparison of vitamin E derivatives alpha-TEA and VES in reduction of mouse mammary tumor burden and metastasis.
abstract: A novel nonhydrolyzable ether derivative of RRR-alpha-tocopherol, RRR-alpha-tocopherol ether acetic acid analog [2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxyacetic acid (alpha-TEA)], and a hydrolyzable ester derivative RRR-alpha-tocopheryl succinate (vitamin E succinate; VES) inhibited BALB/c mouse 66cl-4-GFP mammary tumor cell growth in vitro and in vivo. Treatment of 66cl-4-GFP cells in culture with alpha-TEA or VES induced dose-dependent DNA synthesis arrest and apoptosis and inhibited colony formation. Liposomal formulations of alpha-TEA delivered orally or by aerosol significantly reduced subcutaneous 66cl-4-GFP tumor burden and metastasis to lung and lymph nodes. Liposomal formulations of VES delivered by aerosol significantly reduced tumor burden and lung metastasis, but not lymph node metastasis. Unlike alpha-TEA, VES was ineffective in reducing tumor burden and metastasis to lungs and lymph nodes when administered orally. Analyses of tumor sections showed that alpha-TEA delivered by either method significantly reduced tumor cell proliferation as measured by Ki67, and increased apoptosis as measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL), whereas VES delivered by aerosol reduced tumor cell proliferation and increased apoptosis, but not significantly. In summary, the nonhydrolyzable ether vitamin E derivative alpha-TEA was effective in reducing tumor burden and metastasis when delivered either by aerosol or orally, whereas the hydrolyzable ester vitamin E derivative VES was effective only when delivered by aerosol.
authors.affiliation: Division of Nutrition/A2703, University of Texas at Austin, Austin, TX 78712-1097, USA.
authors.forename: Karla A
authors.initials: KA
authors.lastname: Lawson
authors.forename: Kristen
authors.initials: K
authors.lastname: Anderson
authors.forename: Marla
authors.initials: M
authors.lastname: Simmons-Menchaca
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Atkinson
authors.forename: LuZhe
authors.initials: L
authors.lastname: Sun
authors.forename: Bob G
authors.initials: BG
authors.lastname: Sanders
authors.forename: Kimberly
authors.initials: K
authors.lastname: Kline
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D020287:In Situ Nick-End Labeling; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D014810:Vitamin E; C488288:2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid; D024505:Tocopherols