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Antiproliferative Effect of Vitamin A and D Analogues on Adult Human Keratinocytes in vitro

2008; Karger Publishers; Volume: 21; Issue: 4 Linguagem: Inglês

10.1159/000135639

1660-5535

Svetlana Popadić, Zorica Ramić, Ljiljana Medenica, Maja Stojković, Vladimir Trajkovič, Dušan Popadić,

Phytochemical compounds biological activities

<i>Background:</i> 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. <i>Methods:</i> We analyzed the effect of all-<i>trans</i> retinoic acid (all-<i>trans</i> RA), 13-<i>cis</i> retinoic acid (13-<i>cis</i> RA), ergocalciferol and cholecalciferol in keratinocyte cultures established from adult donors, on the cell proliferation by means of [³H]thymidine incorporation and apoptosis after fluorescein diacetate/trypan blue staining. <i>Results:</i> All tested agents exerted a dose-dependent inhibition of keratinocyte proliferation in the concentration range of 1.25–5 µ<i>M</i>. Based on IC₅₀ values, the antiproliferative efficiency was as follows: cholecalciferol > ergocalciferol = all-<i>trans</i> RA > 13-<i>cis</i> 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. <i>Conclusion:</i> 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.