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


CONCLUSIONS
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.
Popadic
S
S
Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Belgrade, Serbia.
Ramic
Z
Z
Medenica
L
L
Mostarica Stojkovic
M
M
Trajković
V
V
Popadic
D
D
D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004872:Ergocalciferols / Q000494:pharmacology; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology*
D004872:Ergocalciferols; D014801:Vitamin A; D014807:Vitamin D; D002762:Cholecalciferol; D014212:Tretinoin; D015474:Isotretinoin