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

Wang, Xiufang; Birringer, Marc; Dong, Lan-Feng; Vepřek, Pavel; Low, Pauline; Swettenham, Emma; Stantic, Marina; Yuan, Linhong; Zobalova, Renata; Wu, Kun; Ledvina, M; Ralph, Stephen John; Neužil, Jiřı́

doi:10.1158/0008-5472.can-06-2480

Cited by 88 publications

(78 citation statements)

References 47 publications

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“…For instance, the erbB2 receptor has been targeted with an erbB2 receptor-binding heptapeptide (see Table 1) attached to the pro-apoptotic alpha-tocopheryl succinate (-TOS) [123].…”

Section: Structure-activity Relationship Of Ligandsmentioning

confidence: 99%

Cell-penetrating and cell-targeting peptides in drug delivery

Vivès

Schmidt

Pèlegrin

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

315

272

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During the last decade, the potential of peptides for drug delivery into cells has been highlighted by the discovery of several cell-penetrating peptides (CPPs). CPPs are very efficient in delivering various molecules into cells. However, except in some specific cases, their lack of cell specificity remains the major drawback for their clinical development. At the same time, various peptides with specific binding activity for a given cell line (cell-targeting peptides) have also been reported in the literature. One of the goals of the next years will be to optimize the tissue and cell delivery of therapeutic molecules by means of peptides which combine both targeting and internalization advantages. In this review, we describe the main strategies that are currently in use or likely to be employed in the near future to associate both targeting and delivery properties.

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“…For instance, the erbB2 receptor has been targeted with an erbB2 receptor-binding heptapeptide (see Table 1) attached to the pro-apoptotic alpha-tocopheryl succinate (-TOS) [123].…”

Section: Structure-activity Relationship Of Ligandsmentioning

confidence: 99%

Cell-penetrating and cell-targeting peptides in drug delivery

Vivès

Schmidt

Pèlegrin

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

315

272

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“…Tumours were quantified by USI using the Vevo770 device fitted with the RMV704 scan-head (VisualSonics) operated at 60 MHz and with 40 mm resolution Wang et al, 2007). Mice received 10 mmol a-TOS in corn oil/4% ethanol or the vehicle administered i.p.…”

Section: Animal Experimentsmentioning

confidence: 99%

α-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II

et al. 2008

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a-Tocopheryl succinate (a-TOS) is a selective inducer of apoptosis in cancer cells, which involves the accumulation of reactive oxygen species (ROS). The molecular target of a-TOS has not been identified. Here, we show that a-TOS inhibits succinate dehydrogenase (SDH) activity of complex II (CII) by interacting with the proximal and distal ubiquinone (UbQ)-binding site (Q P and Q D , respectively). This is based on biochemical analyses and molecular modelling, revealing similar or stronger interaction energy of a-TOS compared to that of UbQ for the Q P and Q D sites, respectively. CybL-mutant cells with dysfunctional CII failed to accumulate ROS and underwent apoptosis in the presence of a-TOS. Similar resistance was observed when CybL was knocked down with siRNA. Reconstitution of functional CII rendered CybL-mutant cells susceptible to a-TOS. We propose that a-TOS displaces UbQ in CII causing electrons generated by SDH to recombine with molecular oxygen to yield ROS. Our data highlight CII, a known tumour suppressor, as a novel target for cancer therapy.

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“…The LTVSPWY peptide (LTV peptide) is a targeting peptide. It can deliver antisense oligonucleotides and small molecules to cancer cells in vitro [104,105]. Furthermore, various fusion proteins carrying the LTV peptide have been designed to target cancer cells in vitro and in vivo [106].…”

Section: Ltv Gr and Bombesinmentioning

confidence: 99%

Design and Modification of Anticancer Peptides

Hu¹,

Chen²,

Zhao³

et al. 2016

Drug Des

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Cancer is a great concern in the public health and development of novel therapeutic agent or strategy become urgently. Anticancer peptides (ACPs) have become promising anticancer drug candidate molecules due to their several extraordinary properties, such as small size, high activity, low immunogenicity, good biocompatibility, diversity of sequence and more modification sites for the functional molecules. However, the low stability and short half-life of peptides are the major barriers for the application. In this review, we focus on the methods of peptide design and modification to improve the stability, half-life time and specificity of ACPs, which including amino acid substitution, cyclization, hybridization, fragmentization, modification of C-and N-terminal of peptide by polymer or targeting molecules, etc.modification of C-and N-terminal of peptide by polymer or targeting molecules, etc. The schematic diagram of major design and modification strategies of ACPs are shown in Figure 1.

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

Cited by 88 publications

References 47 publications

Cell-penetrating and cell-targeting peptides in drug delivery

Cell-penetrating and cell-targeting peptides in drug delivery

α-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II

Design and Modification of Anticancer Peptides

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