Low doses amino-bisphosphonates stimulate keratinocytes growth inactivating glucocorticoid receptor

Eur J Pharmacol. 2013 Dec 5;721(1-3):301-4. doi: 10.1016/j.ejphar.2013.08.044. Epub 2013 Sep 21.

Abstract

Amino-bisphosphonates (N-BPs) have a wide range of clinical applications to treat bone diseases. Their activity lowered farnesyl pyrophosphate (FPP) endogenous levels by inhibiting FPP synthase. In epithelial cells it has been demonstrated that FPP reduces both cell proliferation and migration activting glucocorticoid receptor. In this study two N-BPs (zoledronate and neridronate) used at low concentrations (100 nM to 10 μM) are able to stimulate human keratinocytes proliferation reducing glucocorticoid receptor activation.

Keywords: Amino-bisphosphonate; Glucocorticoid receptor; Human keratinocyte.

MeSH terms

  • Adult
  • Cell Line
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Keratinocytes / cytology*
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Organophosphonates / pharmacology*
  • Polyisoprenyl Phosphates / metabolism
  • Receptors, Glucocorticoid / agonists
  • Receptors, Glucocorticoid / metabolism*
  • Sesquiterpenes / metabolism

Substances

  • Organophosphonates
  • Polyisoprenyl Phosphates
  • Receptors, Glucocorticoid
  • Sesquiterpenes
  • farnesyl pyrophosphate