%0 Journal Article
%T The vitamin E analog, alpha-tocopheryloxyacetic acid enhances the anti-tumor activity of trastuzumab against HER2/neu-expressing breast cancer
%A Tobias Hahn
%A Deborah J Bradley-Dunlop
%A Laurence H Hurley
%A Daniel Von-Hoff
%A Stephen Gately
%A Disis L Mary
%A Hailing Lu
%A Manuel L Penichet
%A David G Besselsen
%A Brook B Cole
%A Tanisha Meeuwsen
%A Edwin Walker
%A Emmanuel T Akporiaye
%J BMC Cancer
%D 2011
%I BioMed Central
%R 10.1186/1471-2407-11-471
%X In this study we examined the effect of ¦Á-TEA plus HER2/neu-specific antibody treatment on HER2/neu-expressing breast cancer cells in vitro and in a HER2/neu positive human xenograft tumor model in vivo.We show in vitro that ¦Á-TEA plus anti-HER2/neu antibody has an increased cytotoxic effect against murine mammary tumor cells and human breast cancer cells and that the anti-tumor effect of ¦Á-TEA is independent of HER2/neu status. More importantly, in a human breast cancer xenograft model, the combination of ¦Á-TEA plus trastuzumab resulted in faster tumor regression and more tumor-free animals than trastuzumab alone.Due to the cancer cell selectivity of ¦Á-TEA, and because ¦Á-TEA kills both HER2/neu positive and HER2/neu negative breast cancer cells, it has the potential to be effective and less toxic than existing chemotherapeutic drugs when used in combination with HER2/neu antibody.Alpha-tocopheryloxyacetic acid (¦Á-TEA) is an ether derivative of naturally occurring vitamin E (alpha-tocopherol). Unlike vitamin E, which lacks in vivo anti-tumor activity and fails to prevent cancer in humans [1,2], ¦Á-TEA is directly cytotoxic to tumor cells [3-7] via a mechanism that includes mitochondrial depolarization and generation of reactive oxygen species leading to apoptotic cell death [8-10] as has been reported for alpha-tocopheryl succinate (¦Á-TOS) [11]. Unlike alpha-tocopheryl succinate (¦Á-TOS), which is susceptible to conversion to the apoptosis-inert tocopherol and succinic acid by intestinal esterases, ¦Á-TEA is stable and induces apoptosis of a variety of mouse and human cancer cell lines while sparing normal cells [3,4,6,7]. More importantly, we reported recently that oral ¦Á-TEA significantly inhibited the growth of transplanted murine breast cancer (4T1) and dramatically reduced the incidence of lung metastases [7] and was able to suppress growth in a clinically relevant spontaneous model of breast cancer (MMTV-PyMT) without overt toxicity [6].HER2/neu is a proto-oncoge
%U http://www.biomedcentral.com/1471-2407/11/471