title: Valrubicin in a topical formulation treats psoriasis in a xenograft transplantation model.
abstract: 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.
authors.affiliation: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark. cecilia.kjeldsen@ki.au.dk
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rosada
authors.forename: Karin
authors.initials: K
authors.lastname: Stenderup
authors.forename: Elisabeth
authors.initials: E
authors.lastname: de Darkó
authors.forename: Frederik
authors.initials: F
authors.lastname: Dagnaes-Hansen
authors.forename: Søren
authors.initials: S
authors.lastname: Kamp
authors.forename: Tomas Norman
authors.initials: TN
authors.lastname: Dam
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D011565:Psoriasis / Q000188:drug therapy*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; C016163:valrubicin; D004317:Doxorubicin