Novel fusion protein derived from vasostatin 30 and vasoinhibin II-14.1 potently inhibits coronary endothelial cell proliferation

Mol Biotechnol. 2013 Jul;54(3):920-9. doi: 10.1007/s12033-012-9642-4.

Abstract

Angiogenesis has been considered an important target for cancer therapy. The inhibition of angiogenesis represents a promising strategy for anti-cancer treatment, tumor growth inhibition, and metastasis. Vasostatin 30 (Vs30), and the 14.1 kDa vasoinhibin (Vi-II-14.1) are two peptides with remarkable anti-tumor and anti-angiogenic effect. The aim of this study was to produce a novel fusion protein between Vs30 and Vi-II-14.1, denominated VS_VI, to obtain a new protein with higher biological activity. The protein fusion genes were cloned into a T7 promoter-based vector, expressed in Escherichia coli BL21-SI and purified by affinity column chromatography. In vitro assays showed that the recombinant fusion protein inhibited rat coronary endothelial cell proliferation at 65.5 % at 10 nM, whereas recombinant Vs30 and Vi-II-14.1 inhibited at 33 and 50.5 % respectively, at the same concentration. The results showed that VS_VI is significantly more active than the Vs30 and Vi-II-14.1 separately. In addition, a practical classification of the vasoinhibins based on the peptide origin and theoretical molecular weight is proposed. This is the first study to produce a new fusion protein derived from Vs30 and Vi-II-14.1, both of them proposed as promising therapeutic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / genetics
  • Angiogenesis Inhibitors / metabolism
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Calreticulin / chemistry
  • Calreticulin / genetics
  • Calreticulin / metabolism
  • Calreticulin / pharmacology*
  • Cell Proliferation / drug effects
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Escherichia coli / genetics
  • Genetic Vectors / genetics
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Prolactin / chemistry
  • Prolactin / genetics
  • Prolactin / metabolism
  • Prolactin / pharmacology*
  • Rats
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacology*

Substances

  • Angiogenesis Inhibitors
  • Calreticulin
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Prolactin