Antitumor activity of opiorphin, sialorphin and their conjugates with a peptide klaklakklaklak

J Pept Sci. 2016 Nov;22(11-12):723-730. doi: 10.1002/psc.2936. Epub 2016 Nov 9.

Abstract

This is the study on the effect of opiorphin, sialorphin and their analogs on antitumor activity. We demonstrated that conjugation of opiorphin and sialorphin with a proapoptotic, antimicrobial peptide klak (klaklakklaklak) led to compounds (opio-klak and sialo-klak) that were cytotoxic against cancer cells (LN18, PC3, A549, HCT116 and B10-F16) in the MTT test. The conjugated analogs were designed to increase the effectiveness of the peptide. The opio-klak derivative was the most effective in the in vitro assays and led to a decrease in viability of cancer cells over time as compared with that of untreated controls. In contrast, treatment with either the untargeted klak peptide or opiorphin as a negative control led to a negligible loss in viability. Antitumor effect of the opio-klak was also observed in vivo in murine melanoma tumor-bearing mice. Cessation of peptide administration resulted in tumor regrowth. Our results are seemingly valuable for the development of opiorphin analogs with potential clinical applications. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Keywords: antitumor activity; circular dichroism; melanoma; opiorphin; peptide synthesis; sialorphin.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antimicrobial Cationic Peptides / chemical synthesis
  • Antimicrobial Cationic Peptides / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / drug effects
  • Female
  • Humans
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Oligopeptides / chemical synthesis
  • Oligopeptides / pharmacology*
  • Protein Precursors / chemical synthesis
  • Protein Precursors / pharmacology*
  • Salivary Proteins and Peptides / chemical synthesis
  • Salivary Proteins and Peptides / pharmacology*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Solid-Phase Synthesis Techniques
  • Tumor Burden / drug effects

Substances

  • Antimicrobial Cationic Peptides
  • Antineoplastic Agents
  • Oligopeptides
  • Protein Precursors
  • Salivary Proteins and Peptides
  • Smr3b protein, rat
  • glutaminyl-arginyl-phenylalanyl-seryl-arginine