Orally active α-tocopheryloxyacetic acid suppresses tumor growth and multiplicity of spontaneous murine breast cancer

Tobias Hahn, Karen Fried, Laurence H. Hurley, Emmanuel T. Akporiaye

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

We recently demonstrated the antitumor efficacy of orally administered α-tocopheryloxyacetic acid (α-TEA), a redox silent and nonhydrolyzable derivative of naturally occurring vitamin E. In order to move α-TEA closer to the clinic to benefit patients with breast cancer, the present study had two goals. First, to determine the minimal effective treatment dose; and second, to test the efficacy of dietary administration of α-TEA in the clinically relevant MMTV-PyMT mouse model of spontaneous breast cancer that more closely resembles human disease. The minimal effective dose of α-TEA was evaluated in the transplantable 4T1 tumor model and we show a dose-dependent decrease of primary tumor growth and reduction of metastatic spread to the lung. Six-week-old MMTV-PyMT mice were treated with oral α-TEA for 9 weeks, with no apparent signs of drug toxicity. The α-TEA treatment delayed tumor development and significantly slowed tumor progression, resulting in a 6-fold reduction of the average cumulative tumor size. In addition, oral α-TEA caused an 80% reduction in spontaneous metastases. In situ analysis of tumor tissue identified apoptosis as an important mechanism of α-TEA-mediated tumor suppression in addition to inhibition of tumor cell proliferation. This study shows, for the first time, the ability of orally administered α-TEA to delay tumor onset and to inhibit the progression and metastatic spread of a clinically relevant model of spontaneous breast cancer. Our finding of the high efficacy in this tumor model highlights the translational potential of oral α-TEA therapy.

Original languageEnglish (US)
Pages (from-to)1570-1578
Number of pages9
JournalMolecular Cancer Therapeutics
Volume8
Issue number6
DOIs
StatePublished - Jun 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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