Valrubicin in a Topical Formulation Treats Psoriasis in a Xenograft Transplantation Model

Valrubicin is a cytostatic drug currently approved by the American Federal Drug Administration as a trademarked Valstar sterile solution for the treatment of bladder cancer. Valrubicin has shown an excellent therapeutic potential with minimal toxicity. This study investigated the effect in vivo of t...

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Bibliographic Details
Published in:Journal of investigative dermatology 2010-02, Vol.130 (2), p.455-463
Main Authors: Rosada, Cecilia, Stenderup, Karin, de Darkó, Elisabeth, Dagnaes-Hansen, Frederik, Kamp, Søren, Dam, Tomas Norman
Format: Article
Language:English
Subjects:
Administration, Topical
Adult
Aged
Animals
Antineoplastic Agents - administration & dosage
Biological and medical sciences
Cell Line, Tumor
Cell Proliferation
Dermatology
Doxorubicin - administration & dosage
Doxorubicin - analogs & derivatives
Epidermis - metabolism
Humans
Keratinocytes - metabolism
Medical sciences
Mice
Mice, SCID
Middle Aged
Neoplasm Transplantation
Psoriasis - drug therapy
Psoriasis. Parapsoriasis. Lichen
Urinary Bladder Neoplasms - drug therapy
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Summary:Valrubicin is a cytostatic drug currently approved by the American Federal Drug Administration as a trademarked Valstar sterile solution for the treatment of bladder cancer. Valrubicin has shown an excellent therapeutic potential with minimal toxicity. This study investigated the effect in vivo of treating psoriasis with a daily topical application of valrubicin cream in a psoriasis xenograft transplantation model. Psoriasis is characterized by an accelerated keratinocyte proliferation, resulting in increased epidermal thickness. We thus studied the cytostatic potential of valrubicin on epidermal keratinocytes. In vivo, valrubicin treatment resulted in a normalization of epidermal morphology and a reduction in epidermal thickness after 12 days. In addition, the dermal vessel pattern was reduced and the stratum granulosum was regained. Staining for a regenerative proliferation marker showed a decrease in keratinocyte proliferation, and scattered epidermal cells showed apoptosis. In vitro, valrubicin was shown to localize solely to the cell cytoplasm in cultured keratinocytes and to reduce keratinocyte proliferation as well as increase apoptosis by activation of caspases 3, 7, and 9. Our results indicated that valrubicin successfully treats psoriasis in a xenograft transplantation model, suggesting that topical valrubicin may become an upcoming treatment for psoriasis.
ISSN:0022-202X
1523-1747
DOI:10.1038/jid.2009.277