title: Topical application of bleaching phenols; in-vivo studies and mechanism of action relevant to melanoma treatment.
abstract: Skin depigmentation represents a well-established treatment for extensive vitiligo and may likewise be suited to prevent tumor recurrences and as a prophylactic treatment of familial melanoma, as common bleaching agents are cytotoxic to melanocytes. Effective melanoma prevention requires a bleaching agent-induced loss of exposed melanocytes supported by an immune response to distant pigment cells. Studies on human explant cultures treated with depigmenting agents such as 4-tertiary butyl phenol (4-TBP) or monobenzyl ether of hydroquinone (MBEH) showed a significant increase in the migration of Langerhans cells toward the dermis only upon treatment with MBEH, thus suggesting selective elicitation of an immune response. To assess the depigmenting potential of bleaching agents in vivo, 4-TBP and MBEH were topically applied to C57BL/6 wild type as well as k14-SCF transgenic, epidermally pigmented mice. MBEH-induced significant skin depigmentation in both strains was not observed upon treatment with 4-TBP. Cytokine expression patterns in skin treated with MBEH support activation of a Th1-mediated immune response corresponding to an influx of T cells and macrophages. Importantly, despite insensitivity of tumor cells to MBEH-induced cytotoxicity, significantly retarded tumor growth was observed in B16 challenged k14-SCF mice pretreated with MBEH, likely due to an abundance of cytotoxic T cells accompanied by an increased expression of Th1 and Th17 cytokines. These data support the use of MBEH as a prophylactic treatment for melanoma.
authors.affiliation: Molecular and Cellular Biochemistry Graduate Program, Loyola University Medical Center, 2160 S. 1st Avenue, Chicago, IL 60153, USA.
authors.forename: Vidhya
authors.initials: V
authors.lastname: Hariharan
authors.forename: Timothy
authors.initials: T
authors.lastname: Toole
authors.forename: Jared
authors.initials: J
authors.lastname: Klarquist
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Mosenson
authors.forename: B Jack
authors.initials: BJ
authors.lastname: Longley
authors.forename: I Caroline
authors.initials: IC
authors.lastname: Le Poole
mesh_terms: D000287:Administration, Topical; D000818:Animals; D057886:Bleaching Agents / Q000008:administration & dosage; D045744:Cell Line, Tumor; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007801:Langerhans Cells / Q000187:drug effects / Q000473:pathology; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010636:Phenols / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D057886:Bleaching Agents; D010636:Phenols