title: A peptide conjugate of vitamin E succinate targets breast cancer cells with high ErbB2 expression.
abstract: 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.
authors.affiliation: Apoptosis Research Group and Genomics Research Centre, School of Medical Science, Griffith University, Southport, Queensland, Australia.
authors.forename: Xiu-Fang
authors.initials: XF
authors.lastname: Wang
authors.forename: Marc
authors.initials: M
authors.lastname: Birringer
authors.forename: Lan-Feng
authors.initials: LF
authors.lastname: Dong
authors.forename: Pavel
authors.initials: P
authors.lastname: Veprek
authors.forename: Pauline
authors.initials: P
authors.lastname: Low
authors.forename: Emma
authors.initials: E
authors.lastname: Swettenham
authors.forename: Marina
authors.initials: M
authors.lastname: Stantic
authors.forename: Lin-Hong
authors.initials: LH
authors.lastname: Yuan
authors.forename: Renata
authors.initials: R
authors.lastname: Zobalova
authors.forename: Kun
authors.initials: K
authors.lastname: Wu
authors.forename: Miroslav
authors.initials: M
authors.lastname: Ledvina
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ralph
authors.forename: Jiri
authors.initials: J
authors.lastname: Neuzil
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000378:metabolism; D024505:Tocopherols; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D009842:Oligopeptides; D018719:Erb-b2 Receptor Tyrosine Kinases; D024505:Tocopherols; D014810:Vitamin E