科研之友
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摘要
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.
- 出版日期2012-9-1
