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A Peptide Conjugate of Vitamin E Succinate Targets Breast Cancer Cells with High ErbB2 Expression

¹ Apoptosis Research Group and ² Genomics Research Centre, School of Medical Science, Griffith University, Southport, Queensland, Australia; ³ Department of Human Nutrition, Institute of Nutrition, Friedrich-Schiller University, Jena, Germany; ⁴ Institute of Organic Chemistry and Biochemistry and ⁵ Molecular Therapy Group, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic; and ⁶ Department of Food and Nutrition, Harbin Medical University, Harbin, Heilongjiang Province, China

Requests for reprints: Jiri Neuzil, Apoptosis Research Group, School of Medical Science, Griffith Institute of Health and Medical Research, Griffith University Gold Coast Campus, Southport, Queensland, Australia. Phone: 61-7-55529109; Fax: 61-7-55524888; E-mail: j.neuzil{at}griffith.edu.au.

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 -tocopheryl succinate (-TOS). Treating erbB2-low or erbB2-high cells with -TOS induced similar levels of apoptosis, whereas -TOS-LTVSPWY induced greater levels of apoptosis in erbB2-high cells. -TOS rapidly accumulated in erbB2-high cells exposed to -TOS-LTVSPWY. The extent of apoptosis induced in erbB2-high cells by -TOS-LTVSPWY was suppressed by erbB2 RNA interference as well as by inhibition of either endocytotic or lysosomal function. -TOS-LTVSPWY reduced erbB2-high breast carcinomas in FVB/N c-neu transgenic mice. We conclude that a conjugate of a peptide targeting -TOS to erbB2-overexpressing cancer cells induces rapid apoptosis and efficiently suppresses erbB2-positive breast tumors. [Cancer Res 2007;67(7):3337–44]

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