Antiproliferative effect of vitamin A and D analogues on adult human keratinocytes in vitro

Skin Pharmacol Physiol. 2008;21(4):227-34. doi: 10.1159/000135639. Epub 2008 May 29.

Abstract

Background: Vitamin A and D analogues play an important role in epidermal homeostasis and are used in the treatment of various skin diseases. The failure of retinoid and vitamin D treatments is sometimes difficult to explain.

Methods: We analyzed the effect of all-trans retinoic acid (all-trans RA), 13-cis retinoic acid (13-cis RA), ergocalciferol and cholecalciferol in keratinocyte cultures established from adult donors, on the cell proliferation by means of [(3)H]thymidine incorporation and apoptosis after fluorescein diacetate/trypan blue staining.

Results: All tested agents exerted a dose-dependent inhibition of keratinocyte proliferation in the concentration range of 1.25-5 microM. Based on IC(50) values, the antiproliferative efficiency was as follows: cholecalciferol > ergocalciferol = all-trans RA > 13-cis RA. The observed effect of cholecalciferol and ergocalciferol, but not retinoids, involved the induction of apoptotic cell death. Combining vitamins A and D did not further increase the proliferation block and even displayed an antagonistic effect.

Conclusion: The susceptibility of keratinocytes to the antiproliferative action of vitamins A and D was markedly different in cell cultures derived from different donors, indicating a possible predictive value of the in vitro testing for the efficiency of the clinical response to these agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Cholecalciferol / pharmacology
  • Dose-Response Relationship, Drug
  • Ergocalciferols / pharmacology
  • Humans
  • Isotretinoin / pharmacology
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Tretinoin / pharmacology
  • Vitamin A / analogs & derivatives*
  • Vitamin A / pharmacology*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / pharmacology*

Substances

  • Ergocalciferols
  • Vitamin A
  • Vitamin D
  • Cholecalciferol
  • Tretinoin
  • Isotretinoin