α-Tocopheryloxyacetic acid is superior to α-tocopheryl succinate in suppressing HER2-high breast carcinomas due to its higher stability

Authors

  • Lan-Feng Dong,

    Corresponding author
    1. School of Medical Science, Griffith Health Institute, Griffith University, Southport, QLD, Australia
    • Apoptosis Research Group, School of Medical Science and Griffith Health Institute, Griffith University Gold Coast Campus, Southport, Queensland, Australia
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  • Gary Grant,

    1. School of Pharmacy, Griffith Health Institute, Griffith University, Southport, QLD, Australia
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  • Helen Massa,

    1. School of Medical Science, Griffith Health Institute, Griffith University, Southport, QLD, Australia
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  • Renata Zobalova,

    1. School of Medical Science, Griffith Health Institute, Griffith University, Southport, QLD, Australia
    2. Molecular Therapy Group, Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic
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  • Emmanuel Akporiaye,

    1. Earle A. Chiles Research Institute, Providence Portland Medical Centre, Portland, OR
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  • Jiri Neuzil

    Corresponding author
    1. School of Medical Science, Griffith Health Institute, Griffith University, Southport, QLD, Australia
    2. Molecular Therapy Group, Institute of Biotechnology, Czech Academy of Sciences, Prague, Czech Republic
    • Apoptosis Research Group, School of Medical Science and Griffith Health Institute, Griffith University Gold Coast Campus, Southport, Queensland, Australia
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Abstract

Breast cancer is the number one neoplastic disease of women, with the HER2-high carcinomas presenting a considerable challenge for efficient treatment. Therefore, a search for novel agents active against this type of cancer is warranted. We tested two vitamin E (VE) analogs, the esterase-hydrolyzable α-tocopheryl succinate (α-TOS) and the non-hydrolyzable ether α-tocopheryloxyacetic acid (α-TEA) for their effects on HER2-positive breast carcinomas using a breast tumor mouse model and breast cancer cell lines. Ultrasound imaging documented that α-TEA suppressed breast carcinomas in the transgenic animals more efficiently than found for its ester counterpart. However, both agents exerted a comparable apoptotic effect on the NeuTL breast cancer cells derived from the FVB/N c-neu mice as well as in the human MBA-MD-453 and MCF7HER2-18 cells with high level of HER2. The superior anti-tumor effect of α-TEA over α-TOS in vivo can be explained by longer persistence of the former in mice, possibly due to the enhanced plasma and hepatic processing of α-TOS in comparison to the esterase-non-cleavable α-TEA. Indeed, the stability of α-TOS in plasma was inferior to that of α-TEA. We propose that α-TEA is a promising drug efficient against breast cancer, as documented by its effect on experimental HER2-positive breast carcinomas that present a considerable problem in cancer management.

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