Comparison of vitamin E derivatives α-TEA and VES in reduction of mouse mammary tumor burden and metastasis

Karla A. Lawson, Kristen Anderson, Marla Simmons-Menchaca, Jeffrey Atkinson, Lu Zhe Sun, Bob G. Sanders, Kimberly Kline

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

A novel nonhydrolyzable ether derivative of RRR-α-tocopherol, RRR-α-tocopherol ether acetic acid analog [2,5,7,8-tetramethyl-2R-(4R,8R, 12-trimethyltridecyl)chroman-6-yloxyacetic acid (α-TEA)], and a hydrolyzable ester derivative RRR-α-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 α-TEA or VES induced dose-dependent DNA synthesis arrest and apoptosis and inhibited colony formation. Liposomal formulations of α-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 α-TEA, VES was ineffective in reducing tumor burden and metastasis to lungs and lymph nodes when administered orally. Analyses of tumor sections showed that α-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 ́-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.

Original languageEnglish (US)
Pages (from-to)954-963
Number of pages10
JournalExperimental Biology and Medicine
Volume229
Issue number9
DOIs
StatePublished - Oct 2004

Keywords

  • Antitumor agents
  • Metastasis
  • RRR-α-tocopheryl succinate (VES)
  • Syngeneic mouse mammary cancer model
  • Vitamin E analog ́-TEA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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