Implication of limonene and linalyl acetate in cytotoxicity induced by bergamot essential oil in human neuroblastoma cells

Fitoterapia. 2013 Sep;89:48-57. doi: 10.1016/j.fitote.2013.05.014. Epub 2013 May 23.


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.

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.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Citrus / chemistry*
  • Cyclohexenes / pharmacology
  • Cyclohexenes / therapeutic use*
  • Cytoskeleton / drug effects
  • DNA Fragmentation
  • Humans
  • Limonene
  • Monoterpenes / pharmacology
  • Monoterpenes / therapeutic use*
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / metabolism
  • Oils, Volatile / chemistry
  • Oils, Volatile / pharmacology
  • Oils, Volatile / therapeutic use*
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Plant Oils / chemistry
  • Plant Oils / pharmacology
  • Plant Oils / therapeutic use*
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / metabolism
  • Terpenes / pharmacology
  • Terpenes / therapeutic use*


  • Antineoplastic Agents, Phytogenic
  • Cyclohexenes
  • Monoterpenes
  • Oils, Volatile
  • Plant Extracts
  • Plant Oils
  • Terpenes
  • bergamot oil
  • linalyl acetate
  • Limonene
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Caspase 3