Vitamin E conjugate targets her2+ breast cancer cells

[Lani]

Cancer Res. 2007 Apr 1;67(7):3337-44. Links
A Peptide Conjugate of Vitamin E Succinate Targets Breast Cancer Cells with High ErbB2 Expression.

Wang XF,
Birringer M,
Dong LF,
Veprek P,
Low P,
Swettenham E,
Stantic M,
Yuan LH,
Zobalova R,
Wu K,
Ledvina M,
Ralph SJ,
Neuzil J.
Apoptosis Research Group and Genomics Research Centre, School of Medical Science, Griffith University, Southport, Queensland, Australia.
Overexpression of erbB2 is associated with resistance to apoptosis. We explored whether high level of erbB2 expression by cancer cells allows their targeting using an erbB2-binding peptide (LTVSPWY) attached to the proapoptotic alpha-tocopheryl succinate (alpha-TOS). Treating erbB2-low or erbB2-high cells with alpha-TOS induced similar levels of apoptosis, whereas alpha-TOS-LTVSPWY induced greater levels of apoptosis in erbB2-high cells. alpha-TOS rapidly accumulated in erbB2-high cells exposed to alpha-TOS-LTVSPWY. The extent of apoptosis induced in erbB2-high cells by alpha-TOS-LTVSPWY was suppressed by erbB2 RNA interference as well as by inhibition of either endocytotic or lysosomal function. alpha-TOS-LTVSPWY reduced erbB2-high breast carcinomas in FVB/N c-neu transgenic mice. We conclude that a conjugate of a peptide targeting alpha-TOS to erbB2-overexpressing cancer cells induces rapid apoptosis and efficiently suppresses erbB2-positive breast tumors. [Cancer Res 2007;67(7):3337-44].
PMID: 17409443 [PubMed - in process]

[heblaj01]

This Australian group of researchers has done a lot of interesting work on vitamin E succinate in the lab.

For human applications at least two possible problems must be clarified:
1. In vivo it has been shown that ingested vitamin E succinate is split loosing its succinyl end. This might be the reason why most in vivo experiments rely on injection intead of oral consumption for optimal activity.

2. some of the Australian researchers have in previous in vivo animal studies demonstrated that injected vitamin E succinate is converted into regular vitamin E (alpha tocopherol) in the liver.
The difference between the two vitamins is that the latter is an antioxidant while the former is not.
So the mode of action of vitamin E succinate could be quite different in the body depending on location.
This brings back to the controversy about using antioxidants concurrently with cancer treatments such as chemo & radiotherapy.
For those interested Ralph Moss has published a long essay in favor of antioxidants as a reaponse to a review against their use by an M.D.