title: Implication of limonene and linalyl acetate in cytotoxicity induced by bergamot essential oil in human neuroblastoma cells.
abstract: Bergamot (Citrus bergamia, Risso et Poiteau) essential oil (BEO) is a widely used plant extract showing anxiolytic, analgesic and neuroprotective effects in rodents; also, BEO activates multiple death pathways in cancer cells. Despite detailed knowledge of its chemical composition, the constituent/s responsible for these pharmacological activities remain largely unknown. Aim of the present study was to identify the components of BEO implicated in cell death. To this end, limonene, linalyl acetate, linalool, γ-terpinene, β-pinene and bergapten were individually tested in human SH-SY5Y neuroblastoma cultures at concentrations comparable with those found in cytotoxic dilutions of BEO. None of the tested compounds elicited cell death. However, significant cytotoxicity was observed when cells were cotreated with limonene and linalyl acetate whereas no other associations were effective. Only cotreatment, but not the single exposure to limonene and linalyl acetate, replicated distinctive morphological and biochemical changes induced by BEO, including caspase-3 activation, PARP cleavage, DNA fragmentation, cell shrinkage, cytoskeletal alterations, together with necrotic and apoptotic cell death. Collectively, our findings suggest a major role for a combined action of these monoterpenes in cancer cell death induced by BEO.
authors.affiliation: Department of Pharmacy Section of Preclinical and Translational Pharmacology and University Consortium for Adaptive Disorders and Head Pain, University of Calabria, 87036 Rende (Cosenza), Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Russo
authors.forename: Antonella
authors.initials: A
authors.lastname: Ciociaro
authors.forename: Laura
authors.initials: L
authors.lastname: Berliocchi
authors.forename: Maria Gilda Valentina
authors.initials: MG
authors.lastname: Cassiano
authors.forename: Laura
authors.initials: L
authors.lastname: Rombolà
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ragusa
authors.forename: Giacinto
authors.initials: G
authors.lastname: Bagetta
authors.forename: Fabio
authors.initials: F
authors.lastname: Blandini
authors.forename: Maria Tiziana
authors.initials: MT
authors.lastname: Corasaniti
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002957:Citrus / Q000737:chemistry*; D053138:Cyclohexenes / Q000494:pharmacology / Q000627:therapeutic use*; D003599:Cytoskeleton / Q000187:drug effects; D053938:DNA Fragmentation; D006801:Humans; D000077222:Limonene; D039821:Monoterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D009822:Oils, Volatile / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053138:Cyclohexenes; D039821:Monoterpenes; D009822:Oils, Volatile; D010936:Plant Extracts; D010938:Plant Oils; D013729:Terpenes; C068336:bergamot oil; C074463:linalyl acetate; D000077222:Limonene; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3
keywords: BEO; Bergamot essential oil; FDA; Limonene; Linalool; Linalyl acetate; Monoterpenes; Natural products; PARP; PI; bergamot essential oil; fluorescein diacetate; poly-(ADP-ribose) polymerase; propidium iodide