Novel vitamin E analogue decreases syngeneic mouse mammary tumor burden and reduces lung metastasis

Karla A. Lawson, Kristen Anderson, Marla Menchaca, Jeffrey Atkinson, Lu Zhe Sun, Vernon Knight, Brian E. Gilbert, Claudio Conti, Bob G. Sanders, Kimberly Kline

Research output: Contribution to journalArticle

76 Scopus citations

Abstract

A nonhydrolyzable ether analogue of RRR-α-tocopherol, 2,5,7,8-tetramethyl-2R-(4R, 8R, 12-trimethyltridecyl)chroman-6-yloxyacetic acid, called RRR-α-tocopheryloxyacetic acid or RRR-α-tocopherol ether-linked acetic acid analogue (α-TEA), exhibits antitumor activity in vitro and in vivo using a syngeneic BALB/c mouse mammary tumor model (line 66 clone 4 stably transfected with green fluorescent protein). Treatment of cells with 5, 10, and 20 μg/ml α-TEA for 3 days produced 6, 34, and 50% apoptosis, respectively, and treatment of cells with 10 μg/ml for 2, 3, 4, and 5 days produced 20, 35, 47, and 58% apoptosis, respectively. A liposomal formulation of α-TEA administered by aerosol reduced s.c. tumor growth and lung metastasis. α-TEA-treated animals showed a significant decrease in tumor volumes over 17 days of aerosol treatment (P < 0.001). Forty percent of aerosol as well as untreated control mice had visible, macroscopic lung metastases versus none (0%) of the α-TEA-treated mice. On the basis of fluorescence microscopic examination of the surface (top and bottom) of flattened whole left lung lobes, an average of 60 ± 15 and 102 ± 17 versus 11 ± 4 fluorescent microscopic metastases was observed in aerosol control and untreated control versus α-TEA-treated animals, respectively. α-TEA formulated in ethanol + peanut oil (5 mg/mouse/day) delivered by gavage did not reduce s.c. primary tumor burden; however, fluorescent microscopic lung metastases were significantly reduced (P < 0.0021). In summary, α-TEA formulated in liposomes and delivered by aerosol is a potent antitumor agent and reduces lung metastasis.

Original languageEnglish (US)
Pages (from-to)437-444
Number of pages8
JournalMolecular cancer therapeutics
Volume2
Issue number5
StatePublished - May 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Lawson, K. A., Anderson, K., Menchaca, M., Atkinson, J., Sun, L. Z., Knight, V., Gilbert, B. E., Conti, C., Sanders, B. G., & Kline, K. (2003). Novel vitamin E analogue decreases syngeneic mouse mammary tumor burden and reduces lung metastasis. Molecular cancer therapeutics, 2(5), 437-444.