Peptides derived from the copper-binding region of lysyl oxidase exhibit antiangiogeneic properties by inhibiting enzyme activity: an in vitro study

Authors

  • Arun Mohankumar,

    1. R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Medical Research Foundation, Chennai, Tamil Nadu, India
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  • Bhuvanasundar Renganathan,

    1. R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Medical Research Foundation, Chennai, Tamil Nadu, India
    2. Birla Institute of Technology and Science, Pilani, Rajasthan, India
    Current affiliation:
    1. Birla Institute of Technology and Science, Pilani, Rajasthan, India
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  • Coral Karunakaran,

    1. R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Medical Research Foundation, Chennai, Tamil Nadu, India
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  • Subbulakshmi Chidambaram,

    1. R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Medical Research Foundation, Chennai, Tamil Nadu, India
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  • Sulochana Konerirajapuram Natarajan

    Corresponding author
    1. R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Medical Research Foundation, Chennai, Tamil Nadu, India
    • Correspondence to: Sulochana Konerirajapuram Natarajan, R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Medical Research Foundation, Chennai, Tamil Nadu, India. E-mail: drkns@snmail.org

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  • These authors contributed equally to this work.

Abstract

Despite the rigorous research on abnormal angiogenesis, there is a persistent need for the development of new and efficient therapies against angiogenesis-related diseases. The role of Lysyl oxidase (LOX) in angiogenesis and cancer has been established in prior studies. Copper is known to induce the synthesis of LOX, and hence regulates its activity. Hypoxia-induced metastasis is dependent on LOX expression and activity. It has been believed that the inhibition of LOX would be a therapeutic strategy to inhibit angiogenesis. To explore this, we designed peptides (M peptides) from the copper-binding region of LOX and hypothesized them to modulate LOX. The peptides were characterized, and their copper-binding ability was confirmed by mass spectrometry. The M peptides were found to reduce the levels of intracellular copper when the cells were co-treated with copper. The peptides showed promising effect on aortic LOX, recombinant human LOX and LOX produced by human umbilical vein endothelial cells (HUVECs). The study also explores the effect of these peptides on copper and hypoxia-stimulated angiogenic response in HUVECs. It was found that the M peptides inhibited copper/hypoxia-induced LOX activity and inhibited stimulated HUVEC tube formation and migration. This clearly indicated the potential of M peptides in inhibiting angiogenesis, highlighting their role in the formulation of drugs for the same. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

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