A peptide conjugate of Vitamin E succinate targets breast cancer cells with high erbB2 expression
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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 A-tocopheryl succinate (A-TOS). Treating erbB2-low or erbB2-high cells with A-TOSinduced similar levels of apoptosis, whereas A-TOS-LTVSPWY induced greater levels of apoptosis in erbB2- high cells. A-TOSrapidly accumulated in erbB2-high cells exposed to A-TOS-LTVSPWY. The extent of apoptosis induced in erbB2-high cells by A-TOS-LTVSPWY was suppressed by erbB2 RNA interference as well as by inhibition of either endocytotic or lysosomal function. A-TOS-LTVSPWY reduced erbB2-high breast carcinomas in FVB/N c-neu transgenic mice. We conclude that a conjugate of a peptide targeting A-TOSto erbB2-overexpressing cancer cells induces rapid apoptosis and efficiently suppresses erbB2-positive breast tumors.
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