title: In vitro photo-induced cytotoxic activity of Citrus bergamia and C. medica L. cv. Diamante peel essential oils and identified active coumarins.
abstract: BACKGROUND
  The search for innovative therapeutic approaches is gaining more interest in clinical oncology.
  
  
  OBJECTIVE
  In the present investigation we reported the chemical profile and the photo-induced cytotoxic activity of two endemic Calabrian Citrus species (Rutaceae): Citrus bergamia Risso & Poit. and Citrus medica L. cv. Diamante.
  
  
  METHODS
  Essential oils were obtained by hydrodistillation and analyzed by GC and GC/MS. In order to evaluate the cytotoxic activity two melanoma models, such as amelanotic melanoma C32 and malignant melanoma A375, were used.
  
  
  RESULTS
  The essential oil of C. bergamia was characterized by limonene, linalyl acetate, gamma-terpinene, linalool and beta-pinene as major components. The most abundant compounds of C. medica cv. Diamante oil were limonene, gamma-terpinene, citral, geranial, beta-pinene and alpha-pinene. Two coumarins, bergapten and citropten, were also identified in C. bergamia and C. medica cv. Diamante, respectively and tested for biological activity. Both C. bergamia and C. medica cv. Diamante oils exhibited a selective interesting activity against the A375 cell line with IC(50) values of 79.3 and 89.1 microg/mL, respectively, after 100 min exposure to UV irradiation. The strong antiproliferative activity demonstrated with bergapten (IC(50) value of 71.3 microg/mL after 20 min of irradiation) was not found with citropten.
  
  
  CONCLUSIONS
  Our study suggested that UV irradiation is effective in activating essential oils and in particular bergapten. This phototoxicity may be considered as a treatment option in some cases of lentigo maligna or lentigo maligna melanoma.
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy and Nutrition and Health Sciences, University of Calabria, Rende, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Menichini
authors.forename: Rosa
authors.initials: R
authors.lastname: Tundis
authors.forename: Monica Rosa
authors.initials: MR
authors.lastname: Loizzo
authors.forename: Marco
authors.initials: M
authors.lastname: Bonesi
authors.forename: Eugenio
authors.initials: E
authors.lastname: Provenzano
authors.forename: Bruno
authors.initials: B
authors.lastname: de Cindio
authors.forename: Francesco
authors.initials: F
authors.lastname: Menichini
mesh_terms: D000078223:5-Methoxypsoralen; D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002957:Citrus / Q000737:chemistry*; D003374:Coumarins / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects*; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D020128:Inhibitory Concentration 50; D008545:Melanoma / Q000188:drug therapy; D018328:Melanoma, Amelanotic / Q000188:drug therapy; D008730:Methoxsalen / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology / Q000528:radiation effects; D009822:Oils, Volatile / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects*; D010778:Photochemotherapy; D008517:Phytotherapy; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003374:Coumarins; D009822:Oils, Volatile; D000078223:5-Methoxypsoralen; C037446:5,7-dimethoxycoumarin; D008730:Methoxsalen