A peptide conjugate of Vitamin E succinate targets breast cancer cells with high erbB2 expression
Author(s)
Wang, Xiu-Fang
Birringer, Marc
Dong, Lan-Feng
Veprek, Pavel
Low, Pauline
Swettenham, Emma
Stantic, Marina
Yuan, Lin-Hong
Zobalova, Renata
Vu, Kun
Ledvina, Miroslav
Ralph, Stephen J
Neuzil, Jiri
Year published
2007
Metadata
Show full item recordAbstract
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 ...
View more >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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View more >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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Journal Title
Cancer Research
Volume
67
Issue
7
Publisher URI
Copyright Statement
© 2007 AACR. Please refer to the journal link for access to the definitive, published version.
Subject
Oncology and carcinogenesis
Biochemistry and cell biology