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

0383035 - BTÚ 2013 RIV DE eng J - Journal Article
Dong, L. F. - Grant, G. - Massa, H. - Zobalová, Renata - Akporiaye, E. - Neužil, Jiří
alpha-Tocopheryloxyacetic acid is superior to alpha-tocopheryl succinate in suppressing HER2-high breast carcinomas due to its higher stability.
International Journal of Cancer. Roč. 131, č. 5 (2012), s. 1052-1058. ISSN 0020-7136. E-ISSN 1097-0215
R&D Projects: GA ČR GAP301/10/1937; GA AV ČR(CZ) KAN200520703
Institutional research plan: CEZ:AV0Z50520701
Keywords : Breast cancer * vitamin E analogs * apoptosis induction
Subject RIV: CE - Biochemistry
Impact factor: 6.198, year: 2012

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 a-tocopheryl succinate (a-TOS) and the non-hydrolyzable ether a-tocopheryloxyacetic acid (a-TEA) for their effects on HER2-positive breast carcinomas using a breast tumor mouse model and breast cancer cell lines. Ultrasound imaging documented that a-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 a-TEA over a-TOS in vivo can be explained by longer persistence of the former in mice, possibly due to the enhanced plasma and hepatic processing of a-TOS in comparison to the esterase-non-cleavable a-TEA. Indeed, the stability of a-TOS in plasma was inferior to that of a-TEA. We propose that a-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.
Permanent Link: http://hdl.handle.net/11104/0213103