title: Effects of topical corticosteroids on cell proliferation, cell cycle progression and apoptosis: in vitro comparison on HaCaT.
abstract: Topical-corticosteroids are mainly used for the treatment of inflammatory or hyperproliferative skin diseases. The in vivo assay to rank topical-corticosteroids potency, based on the skin blanching, is not adapted to compare their anti-proliferative efficacy. We have compared the antiproliferative effect of six topical-corticosteroids on a model of hyperproliferant keratinocytes (HaCaT). Betamethasone-dipropionate; clobetasol-propionate; betamethasone-valerate; desonide; hydrocortisone-butyrate and hydrocortisone-base, at different concentrations (10(-8)-10(-4)M) have been compared. HaCaT proliferation has been evaluated by MTT-assay and the mechanism of the death was evaluated by annexin V/propidium iodide staining and cell cycle phases analysis. Topical corticosteroids reduced cell growth in a dose-dependent manner. At 10(-4)M, betamethasone dipropionate was the most antiproliferative compound while hydrocortisone-butyrate was the less. Hydrocortisone-base which is usually considered as the less potent topical-corticosteroids showed a clear cytotoxic effect. Betamethasone-dipropionate and betamethasone-valerate induced more apoptosis than necrosis whereas the reverse has been observed for other topical-corticosteroids. All topical-corticosteroids, except clobetasol-propionate, arrested cell cycle mainly in G2-phase. Clobetasol-propionate arrested cell cycle in S-phase population. At 10(-8)M, topical-corticosteroids induced HaCaT proliferation. In terms of antiproliferative effect at 10(-4)M, we propose to rank topical corticosteroids as follow: betamethasone-dipropionate>desonide≥betamethasone-valerate=hydrocortisone-base=clobetasol-propionate>hydrocortisone-butyrate. This classification differs from the current ranking, based on the vasoconstrictive effect, but is more adapted for hyperproliferative disease treatment.
authors.affiliation: Research and Studies Center on the Integument (CERT), Department of Dermatology, Clinical Investigation Center (CIC INSERM 1431), Besançon University Hospital, France; Engineering and Cutaneous Biology Laboratory, INSERM UMR 1098, SFR FED 4234, University of Franche-Comte, Besançon, France. Electronic address: guichard.alexandre@gmail.com.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Guichard
authors.affiliation: Research and Studies Center on the Integument (CERT), Department of Dermatology, Clinical Investigation Center (CIC INSERM 1431), Besançon University Hospital, France; Engineering and Cutaneous Biology Laboratory, INSERM UMR 1098, SFR FED 4234, University of Franche-Comte, Besançon, France. Electronic address: philippe.humbert@univ-fcomte.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Humbert
authors.affiliation: Engineering and Cutaneous Biology Laboratory, INSERM UMR 1098, SFR FED 4234, University of Franche-Comte, Besançon, France. Electronic address: marion.tissot@univ-fcomte.fr.
authors.forename: Marion
authors.initials: M
authors.lastname: Tissot
authors.affiliation: Engineering and Cutaneous Biology Laboratory, INSERM UMR 1098, SFR FED 4234, University of Franche-Comte, Besançon, France. Electronic address: patrice.muret@univ-fcomte.fr.
authors.forename: Patrice
authors.initials: P
authors.lastname: Muret
authors.affiliation: BIOEXIGENCE S.A.S., 8 rue Alfred de Vigny, Besançon, France. Electronic address: bioexigence@wanadoo.fr.
authors.forename: Carole
authors.initials: C
authors.lastname: Courderot-Masuyer
authors.affiliation: Engineering and Cutaneous Biology Laboratory, INSERM UMR 1098, SFR FED 4234, University of Franche-Comte, Besançon, France. Electronic address: celine.viennet@univ-fcomte.fr.
authors.forename: Céline
authors.initials: C
authors.lastname: Viennet
mesh_terms: D000279:Administration, Cutaneous; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D003879:Dermatologic Agents; D005938:Glucocorticoids
keywords: Apoptosis; Cell cycle; HaCaT; Keratinocyte; Proliferation; Topical corticosteroid