title: Effects of bergamot essential oil and its extractive fractions on SH-SY5Y human neuroblastoma cell growth.
abstract: OBJECTIVE
  The goals were to investigate the mechanisms underlying the antiproliferative effects of bergamot essential oil (BEO) and to identify the compounds mainly responsible for its SH-SY5Y cells growth rate inhibition.
  
  
  METHODS
  Five BEO extractive fractions (BEOs) differing in their chemical composition were used. Cell proliferation was determined by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell count assays. Trypan blue exclusion test and Annexin V/PI staining were performed to assess their cytotoxic activity. Genotoxicity was detected by comet assay. The cell cycle was checked cytofluorimetrically. Reactive oxygen species (ROS) and Δψm were measured fluorimetrically. Western blotting analyses for some apoptosis-related proteins were carried out.
  
  
  RESULTS
  Treatment of SH-SY5Y cells with some types of BEOs decreased cell growth rate by a mechanism correlated to both apoptotic and necrotic cell death. Coloured BEOs act by increasing ROS generation, responsible for the drop in Δψm, and modulate p38 and extracellular signal-regulated kinases (ERK ½) mitogen-activated protein kinases, p53, Bcl-2 and Bax signalling pathways. Finally, we identify bergamottin and 5-geranyloxy-7-methoxycoumarin as the bioactive molecules that could play a pivotal role in the antiproliferative effects exerted by coloured BEOs.
  
  
  CONCLUSIONS
  Our study provides novel insights into the field of the antiproliferative effects of BEO, which could be exploited in the context of a multitarget pharmacological strategy.
authors: Department of Drug Sciences and Products for Health, University of Messina, Messina, Italy.
authors: Michele
authors: M
authors: Navarra
authors: Department of Drug Sciences and Products for Health, University of Messina, Messina, Italy.
authors: Nadia
authors: N
authors: Ferlazzo
authors: Department of Drug Sciences and Products for Health, University of Messina, Messina, Italy.
authors: Santa
authors: S
authors: Cirmi
authors: Department of Drug Sciences and Products for Health, University of Messina, Messina, Italy.
authors: Elena
authors: E
authors: Trapasso
authors: IRCCS Centro Neurolesi 'Bonino Pulejo', Messina, Italy.
authors: Placido
authors: P
authors: Bramanti
authors: Department of Drug Sciences and Products for Health, University of Messina, Messina, Italy.
authors: Giovanni Enrico
authors: GE
authors: Lombardo
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Paola Lucia
authors: PL
authors: Minciullo
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Gioacchino
authors: G
authors: Calapai
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.|Institute of Clinical Physiology, IFC CNR, Messina Unit, Messina, Italy.
authors: Sebastiano
authors: S
authors: Gangemi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D020552:Comet Assay; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D011564:Furocoumarins / Q000737:chemistry / Q000494:pharmacology; D019254:Genes, bcl-2 / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy*; D009822:Oils, Volatile / Q000737:chemistry / Q000494:pharmacology*; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000187:drug effects
chemical_list: C442483:5-geranyloxy-7-methoxycoumarin; D000970:Antineoplastic Agents; D003374:Coumarins; D011564:Furocoumarins; D009822:Oils, Volatile; D010938:Plant Oils; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C068336:bergamot oil; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D048049:Extracellular Signal-Regulated MAP Kinases; C068337:bergamottin
keywords: Citrus bergamia; SH-SY5Y cells; antiproliferative activity; bergamot essential oil; complementary and alternative medicine