Vitamin E analogs trigger apoptosis in HER2/erbB2-overexpressing breast cancer cells by signaling via the mitochondrial pathway.

Wang XF, Witting PK, Salvatore BA, Neuzil J.

Apoptosis Research Group, School of Health Science, Griffith University, Southport, Qld, Australia.

Alpha-tocopheryl succinate (alpha-TOS) is a redox-silent vitamin E (VE) analog with high pro-apoptotic and anti-neoplastic activity. Here we investigated whether alpha-TOS and several novel VE analogs kill breast cancer cells over-expressing the anti-apoptotic receptor protein HER2/erbB2. The agents induced apoptosis at comparable levels in both erbB2-low and -high cells. Generation of reactive oxygen species (ROS) preceded mitochondrial destabilization and execution of apoptosis, as evidenced by the anti-apoptotic effects of exogenous superoxide dismutase and mitochondrially targeted coenzyme Q. Dissipation of DeltaPsi(m) was followed by cytochrome c and Smac/Diablo re-localization and caspase-dependent cleavage of death substrate. A resistance to apoptosis for the corresponding rho(0) counterparts confirmed a critical dependency for mitochondria during the induction of apoptosis in breast cancer cells mediated by VE analogs and linked apoptosis to generation of radicals as judged by the delayed accumulation of ROS in the cybrid cell types. We conclude that alpha-TOS causes efficient apoptosis in breast cancer cells independent of their erbB2 status. Since erbB2 is frequently over-expressed in breast cancers and renders the neoplastic disease resistant to established treatment, our findings are of clinical interest.

PMID: 15582575 [PubMed - indexed for MEDLINE]

Hi Kathy,

It will be interesting to see how this pans out.

Vitamin E succinate has been considered for other breast cancers as well. However, one scholarly article I read on it mentioned specifically that the body converted eaten vitamin E succinate into a form of vitamin E that did not curb cancer. It had to be administered intravenously to rats or perhaps modified in a very special way that was under development. I think it was hydrolyzed, but I was undergoing chemo at time and may have had chemo brain.

Kathy:

I found the article intersting. I wish the summary would have told whether the Vitamin E succinate was applied to cells in a petri dish or cells in a test animal and if a test animal was used how was the Vitmain E succinate administered. Was it given IV, in food, etc? I have been taking 400 units of Vitamin E succinate three times a day since I completed my dose dense chemo last May in hopes it might help prevent mets. I am also on Herceptin off-label so I am trying whatever I can. Thanks for your research.

Barbara