Rapana thomasiana hemocyanin modified with ionic liquids with enhanced anti breast cancer activity

Int J Biol Macromol. 2016 Jan:82:798-805. doi: 10.1016/j.ijbiomac.2015.10.031. Epub 2015 Oct 23.

Abstract

This is the first study on the surface modification of a hemocyanin from marine snail Rapana thomasiana (RtH) with series of imidazolium-based amino acid ionic liquids [emim][AA]. We monitored the induced by [emim][AA] conformational changes in RtH molecule and evaluated the effect of these ionic liquids (ILs) on the protein thermal stability. The cytotoxicity of all obtained RtH-[emim][AA] complexes was assessed toward breast cancer cells (MCF-7) and murine fibroblasts (3T3). As a whole, even small amounts of the tested ILs altered the secondary structure of RtH. The thermal denaturation of RtH in presence of [emim][AA] displayed multi-component transitions, which were shifted toward lower temperatures in comparison to those estimated for the native RtH. The profiles of the RtH-IL calorimetric curves show a clear dependence on the structure of the added salts. In addition, all RtH-[emim][AA] complexes exhibited an enhanced antiprofilerative activity of toward MCF-7 cells in comparison to that of the native RtH. The best results are observed for RtH-[emim][Leu], RtH-[emim][Trp] or RtH-[emim][Ile], which applied in concentration of 700 μg/mL inhibited the MCF-7 cell viability (for 24h) by 66, 63 and 53%, respectively. In addition, these IL-RtH complexes were less cytotoxic to 3T3 cells, i.e. they exhibited some cell specificity.

MeSH terms

  • 3T3 Cells
  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms
  • Cell Survival / drug effects
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gastropoda*
  • Hemocyanins / chemistry*
  • Hemocyanins / pharmacology*
  • Humans
  • Ionic Liquids / chemical synthesis
  • Ionic Liquids / chemistry*
  • MCF-7 Cells
  • Mice
  • Protein Stability
  • Spectroscopy, Fourier Transform Infrared
  • Thermodynamics

Substances

  • Antineoplastic Agents
  • Ionic Liquids
  • Hemocyanins