Unveil the Anticancer Potential of Limomene Based Therapeutic Deep Eutectic Solvents

Sci Rep. 2019 Oct 17;9(1):14926. doi: 10.1038/s41598-019-51472-7.

Abstract

Deep eutectic solvents have been recently reported as an interesting alternative to improve the therapeutic efficacy of conventional drugs, hence called therapeutic deep eutectic solvents (THEDES). The main objective of this work was to evaluate the potential of limonene (LIM) based THEDES as new possible systems for cancer treatment. LIM is known to have antitumor activity, however it is highly toxic and cell viability is often compromised, thus this compound is not selective towards cancer cells. Different THEDES based on LIM were developed to unravel the anticancer potential of such systems. THEDES were prepared by gently mixing saturated fatty acids menthol or ibuprofen (IBU) with LIM. Successful THEDES were obtained for Menthol:LIM (1:1), CA:LIM (1:1), IBU:LIM (1:4) and IBU:LIM(1:8). The results indicate that all the THEDES present antiproliferative properties, but IBU:LIM (1:4) was the only formulation able to inhibit HT29 proliferation without comprising cell viability. Therefore, IBU:LIM (1:4) was the formulation selected for further assessment of anticancer properties. The results suggest that the mechanism of action of LIM:IBU (1:4) is different from isolated IBU and LIM, which suggest the synergetic effect of DES. In this work, we unravel a methodology to tune the selectivity of LIM towards HT29 cell line without compromising cell viability of healthy cells. We demonstrate furthermore that coupling LIM with IBU leads also to an enhancement of the anti-inflammatory activity of IBU, which may be important in anti-cancer therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Caco-2 Cells
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Decanoic Acids / chemistry
  • Decanoic Acids / pharmacology
  • Decanoic Acids / therapeutic use
  • Drug Compounding / methods
  • Drug Screening Assays, Antitumor
  • HT29 Cells
  • Humans
  • Ibuprofen / chemistry
  • Ibuprofen / pharmacology
  • Ibuprofen / therapeutic use
  • Ionic Liquids / chemistry
  • Ionic Liquids / pharmacology*
  • Ionic Liquids / therapeutic use
  • Limonene / chemistry
  • Limonene / pharmacology*
  • Limonene / therapeutic use
  • Menthol / chemistry
  • Menthol / pharmacology
  • Menthol / therapeutic use
  • Myristic Acid / chemistry
  • Myristic Acid / pharmacology
  • Myristic Acid / therapeutic use
  • Neoplasms / drug therapy*
  • Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Decanoic Acids
  • Ionic Liquids
  • Myristic Acid
  • Menthol
  • decanoic acid
  • Limonene
  • Ibuprofen