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.
Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Belgrade, Serbia.
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Popadic
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Ramic
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Medenica
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Mostarica Stojkovic
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Trajković
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Popadic
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