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Inhibition of cancer cell proliferation by designed peptide amphiphiles

Lookup NU author(s): Lorenzo Aulisa, Dr Nicolas Forraz, Professor Colin McGuckin

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Abstract

HOX genes encode conserved transcription factors that control the morphological diversification along the anteroposterior body axis. HOX proteins bind to DNA through a highly conserved 60 amino acid sequence called the homeodomain, and greater DNA binding specificity and stability are achieved when it forms complexes with cofactors such as PBX and MEIS in humans. In particular, HOX proteins from paralog groups 1-8, interact with PBX proteins via a specific and highly conserved hydrophobic six amino acid sequence localized in the N-terminal region of HOX. In several oncogenic transformations, deregulated HOX gene expression has been observed, indicating an involvement of these transcriptional regulators in carcinogenesis and metastasis. Inhibition of the HOX-PBX interaction could be a strategy to control the abnormal proliferation of these cancer cells. In this study we describe a small designed peptide amphiphile (PA) which self-assembles into micelles and shows inhibition of T3M4 pancreatic cancer cells, K562 leukemia cells and MJT1 melanoma cells while non-cancerous fibroblast NIH 3T3 cells are less affected. This molecule contains three critical regions: a 9-amino-acid sequence designed to disrupt HOX/PBX/DNA complex formation, a 16-amino-acid sequence to deliver the peptide into the cell and a t6-carbon-acyl chain which we show leads to the molecule's self-assembly and significantly enhances the effectiveness of the molecule to slow cell proliferation. (c) 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Publication metadata

Author(s): Aulisa L, Forraz N, McGuckin C, Hartgerink JD

Publication type: Article

Publication status: Unknown

Journal: Acta Biomaterialia

Year: 2009

Volume: 5

Issue: 3

Pages: 842-853

ISSN (print): 1742-7061

ISSN (electronic): 1878-7568

Publisher: Elsevier BV

URL: .http:/dx.doi.org/10.1016/j.actbio.2008.11.002

DOI: 10.1016/j.actbio.2008.11.002


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