Vorinostat, a histone deacetylase inhibitor, as a potential novel treatment for psoriasis

Liat Samuelov, Ron Bochner, Lee Magal, Kiril Malovitski, Nadav Sagiv, Janna Nousbeck, Aviad Keren, Dana Fuchs-Telem, Ofer Sarig, Amos Gilhar, Eli Sprecher*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Psoriasis is characterized by aberrant activation of several pro-inflammatory circuits as well as abnormal hyperproliferation and dysregulated apoptosis of keratinocytes (KCs). Most currently available therapeutic options primarily target psoriasis-associated immunological defects rather than epidermal abnormalities. Objective: To investigate the efficacy of the histone deacetylase (HDAC) inhibitor, Vorinostat, in targeting hyperproliferation and impaired apoptosis in psoriatic skin. Methods: Vorinostat effect was investigated in primary KCs cell cultures using cell cycle analysis by flow cytometry, apoptosis assays (Annexin V-FICH and caspase-3/7) and antibody arrays, qRT-PCR and immunohistochemistry. Vorinostat impact on clinical manifestations of psoriasis was investigated in a chimeric mouse model. Results: Vorinostat was found to inhibit KCs proliferation and to induce their differentiation and apoptosis. Using a chimeric mouse model, vorinostat was found to result in marked attenuation of a psoriasiform phenotype with a significant decrease in epidermal thickness and inhibition of epidermal proliferation. Conclusions: Our results support the notion that vorinostat, a prototypic HDAC inhibitor, may be of potential use in the treatment of psoriasis and other hyperproliferative skin disorders.

Original languageEnglish
Pages (from-to)567-576
Number of pages10
JournalExperimental Dermatology
Volume31
Issue number4
DOIs
StatePublished - Apr 2022

Funding

FundersFunder number
Israel Science Foundation
Ministry of Industry, Trade and Labor

    Keywords

    • Vorinostat
    • chimeric mice
    • histone deacetylase inhibitor
    • histone deacetylases
    • hyperproliferation
    • psoriasis

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