title: Prevention of Photocarcinogenesis by Agonists of 5-HT1A and Antagonists of 5-HT2A Receptors.
abstract: Exposure to UV radiation is the principal cause of nonmelanoma skin cancer, a process in which serotonin (5-HT) is intimately involved. This review focuses on the potential of serotonin receptors, namely 5-HT1/2A, as therapeutic targets for prevention of photocarcinogenesis. UV-induced immunosuppression is triggered by a cascade of events initiated when cis-urocanic acid, a UV photoreceptor present in the skin, binds to the serotonin receptor. Serotonin receptor antagonists will therefore attempt to block this association, and in turn, prevent skin cancer induction. In addition, 5-HT2A receptor antagonists are also capable of regulating DNA repair, including the acceleration of nucleotide excision repair. At the same time, UV-induced formation of reactive oxygen species is also reduced by these agents. Since the involvement of serotonin in photocarcinogenesis process is somewhat underexplored as a pertinent therapeutic effect, this review intends to reveal the use of serotonergic drugs as an important strategy to prevent and/or inhibit photocarcinogenesis. Considering the emergency of developing novel therapeutic strategies for skin cancer management, the use of these agents, whose benefits have partially been studied, may be crucial especially if topically applied. Topical nanoformulations containing serotonin receptor agonists and/or antagonists also represent a pioneer concept in this area. Graphical Abstract ᅟ.
authors.affiliation: Faculdade de Farmácia da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Ana Catarina
authors.initials: AC
authors.lastname: Menezes
authors.affiliation: Nanomedicine and Drug Delivery Systems group of iMed.UL, Lisbon, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Raposo
authors.affiliation: Nanomedicine and Drug Delivery Systems group of iMed.UL, Lisbon, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Simões
authors.affiliation: Nanomedicine and Drug Delivery Systems group of iMed.UL, Lisbon, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Ribeiro
authors.affiliation: Department Biology, Laboratory of Biotechnology and Cytomics, CESAM, Universidade de Aveiro, Aveiro, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Oliveira
authors.affiliation: Nanomedicine and Drug Delivery Systems group of iMed.UL, Lisbon, Portugal. andreiaascenso@ff.ul.pt.
authors.forename: Andreia
authors.initials: A
authors.lastname: Ascenso
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000473:pathology*; D006801:Humans; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000627:therapeutic use*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000627:therapeutic use*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D058825:Serotonin 5-HT1 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A
keywords: DNA repair and cells proliferation; Immunomodulation; Photocarcinogenesis; Serotonin; Serotonin receptors agonists and antagonists