title: An apolar Pistacia lentiscus L. leaf extract: GC-MS metabolic profiling and evaluation of cytotoxicity and apoptosis inducing effects on SH-SY5Y and SK-N-BE(2)C cell lines.
abstract: In the course of a cytotoxicity screening of Mediterranean plants vs. neuroblastoma cells, Pistacia lentiscus was of interest. Pl-C extract, prepared from dried leaves by ultrasound assisted maceration (UAM) in chloroform, was profiled through using GC-MS techniques. To evaluate Pl-C cytotoxicity towards SH-SY5Y and SK-N-BE(2)-C cell lines, MTT, SRB and LDH assays were performed. The caspase-3 activation, DNA fragmentation, as well as micronucleation, were also evaluated. The Pl-C oxidant/antioxidant ability was estimated using different methods. The extract, rich in pentacyclic triterpenes, inhibited mitochondrial redox activity and cell viability of the tested cell lines. LDH assay established that Pl-C did not affect the cell membrane integrity. Indeed, it was able to activate caspase-3 and to cause a ladder pattern of DNA. Western blotting analysis showed that Pl-C processed caspase-3 providing two cleavage products of approximately 20 and 17-kDa, whose densitometric evaluation highlighted that Pl-C was more effective than vinblastine by 3-fold. The pro-apoptotic effect could be related to a disturbance in cell redox balance. In fact, it increased intracellular ROS production, GSSG/GSH ratio and the formation of lipoperoxidation products. The data obtained prompted to further investigate and assess the in vivo efficacy of Pl-C to prevent and/or treat neuroblastoma.
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Science and Technology, Second University of Naples, via Vivaldi, 43, I-81100 Caserta, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Piccolella
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Science and Technology, Second University of Naples, via Vivaldi, 43, I-81100 Caserta, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Nocera
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Science and Technology, Second University of Naples, via Vivaldi, 43, I-81100 Caserta, Italy.
authors.forename: Petronia
authors.initials: P
authors.lastname: Carillo
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Science and Technology, Second University of Naples, via Vivaldi, 43, I-81100 Caserta, Italy.
authors.forename: Pasqualina
authors.initials: P
authors.lastname: Woodrow
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Science and Technology, Second University of Naples, via Vivaldi, 43, I-81100 Caserta, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Greco
authors.affiliation: Department of Physics, University of Naples Federico II, via Cintia, I-80126 Naples, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Manti
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Science and Technology, Second University of Naples, via Vivaldi, 43, I-81100 Caserta, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fiorentino
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Science and Technology, Second University of Naples, via Vivaldi, 43, I-81100 Caserta, Italy. Electronic address: severina.pacifico@unina2.it.
authors.forename: Severina
authors.initials: S
authors.lastname: Pacifico
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D055432:Metabolomics / Q000379:methods; D008928:Mitochondria / Q000378:metabolism; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D027927:Pistacia / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D053148:Caspase 3
keywords: Apoptosis-inducing effects; Cytotoxicity; GC-MS; Pentacyclic triterpenes; Pistacia lentiscus L.; Pro-oxidant activity