Encapsulation of a TRPM8 Agonist, WS12, in Lipid Nanocapsules Potentiates PC3 Prostate Cancer Cell Migration Inhibition through Channel Activation

Sci Rep. 2019 May 28;9(1):7926. doi: 10.1038/s41598-019-44452-4.

Abstract

In prostate carcinogenesis, expression and/or activation of the Transient Receptor Potential Melastatin 8 channel (TRPM8) was shown to block in vitro Prostate Cancer (PCa) cell migration. Because of their localization at the plasma membrane, ion channels, such as TRPM8 and other membrane receptors, are promising pharmacological targets. The aim of this study was thus to use nanocarriers encapsulating a TRPM8 agonist to efficiently activate the channel and therefore arrest PCa cell migration. To achieve this goal, the most efficient TRPM8 agonist, WS12, was encapsulated into Lipid NanoCapsules (LNC). The effect of the nanocarriers on channel activity and cellular physiological processes, such as cell viability and migration, were evaluated in vitro and in vivo. These results provide a proof-of-concept support for using TRPM8 channel-targeting nanotechnologies based on LNC to develop more effective methods inhibiting PCa cell migration in zebrafish xenograft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilides / administration & dosage
  • Anilides / pharmacology*
  • Cell Migration Inhibition / drug effects*
  • Humans
  • Lipids / chemistry
  • Male
  • Menthol / administration & dosage
  • Menthol / analogs & derivatives*
  • Menthol / pharmacology
  • Nanocapsules / chemistry
  • PC-3 Cells
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • TRPM Cation Channels / agonists*
  • TRPM Cation Channels / metabolism

Substances

  • Anilides
  • Lipids
  • N-(4-methoxyphenyl)-4-menthone-3-carboxamide
  • Nanocapsules
  • TRPM Cation Channels
  • TRPM8 protein, human
  • Menthol