title: 1,25-Dihydroxyvitamin D3 and its synthetic derivatives MC903 and EB1089 induce a partial tumoral phenotype reversal in a skin-equivalent system.
abstract: The antitumoral potency of 1,25-dihydroxyvitamin D3 and its synthetic derivatives MC903, EB1089, and KH1060 was investigated on a tumoral Bowen-like epidermis reconstructed from an immortalized human keratinocyte cell line transfected by expression vectors coding for E6 and E7 of human papillomavirus 16. Treatment of skin equivalents by vitamin D derivatives (10(-9) M or 10(-12) M) was performed during (from day 1 to day 15 of culture) or after tissue reconstruction (from day 15 to day 30). Pharmacologic effects were evaluated by morphologic and immunohistologic analysis and compared with those of controls (vehicle alone) and with treatment of skin equivalents derived from normal keratinocytes. When performed during epidermal reconstruction, treatment of tumoral skin equivalents induced only minor morphologic and immunohistologic changes. Conversely, when performed after epidermal reconstruction, treatment with 1,25-dihydroxyvitamin D3, MC903, and EB1089 clearly improved the phenotype of treated tissues. Morphologic analysis showed reorganization of epidermal layers with the appearance of a distinct basal layer and of stratified orthokeratotic stratum corneum. Immunohistochemical analysis demonstrated that the terminal differentiation markers profilaggrin and cytokeratin 10 were re-expressed in the treated tissues while absent in controls. Overall, the results indicate that 1,25-dihydroxyvitamin D3, MC903, and EB1089 can induce a partial reversion of the tumoral phenotype in this in vitro model.
authors.affiliation: Laboratoire de Dermatologie Moléculaire, Institut de Génétique Moléculaire, Montpellier, France.
authors.forename: V
authors.initials: V
authors.lastname: Mils
authors.forename: N
authors.initials: N
authors.lastname: Basset-Séguin
authors.forename: J P
authors.initials: JP
authors.lastname: Molès
authors.forename: J J
authors.initials: JJ
authors.lastname: Guilhou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D010641:Phenotype; D012867:Skin / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; C055085:calcipotriene; D002117:Calcitriol; C078903:seocalcitol