title: Apoptotic effect of eugenol envolves G2/M phase abrogation accompanied by mitochondrial damage and clastogenic effect on cancer cell in vitro.
abstract: BACKGROUND
  Eugenol (EUG) is a major phenolic compound present in clove whose anti-cancer properties have been demonstrated previously. These anti-cancer properties may involves the modulation of different mechanisms, including α-estrogen receptor (αER) in luminal breast cancer cells, COX-2 inhibition in melanoma cells or p53 and caspase-3 activation in colon cancer cells.
  
  
  OBJECTIVE
  EUG promotes a burst in ROS production causing cell-cycle perturbations, mitochondria toxicity and clastogenesis triggering apoptosis in melanoma breast- and cervix-cancer cells in vitro.
  
  
  METHODS
  Morphological changes were evaluated through the light- and electronic- microscopy. Cell-cycle, ROS, PCNA and Apoptosis was detected by flow cytometry and clastogenicity was evaluated by Comet-assay.
  
  
  RESULTS
  The results obtained herein pointed out that EUG promotes, increasing ROS production leading to abrogation of G2/M of phase of cell-cycle, and consecutively, clastogenesis in vitro. In addition, EUG induces Proliferation Cell Nuclear Antigen (PCNA) downregulation and decreasing in mitochondria potential (ΔΨm). Of note, a Bax up-regulation was also observed on cells treated with EUG. All of these findings cooperate in order to induce apoptosis in cancer cells.
  
  
  CONCLUSIONS
  These promising results presented herein shed new light on the mechanisms of action of EUG suggesting a possible applicability of this phenylpropanoid as adjuvant in anti-cancer therapy.
authors.affiliation: Laboratory of Genetics, Butantan Institute, Sao Paulo, SP, Brazil, . Electronic address: paulsaj2001@yahoo.com.br.
authors.forename: Paulo Luiz de Sá
authors.initials: PL
authors.lastname: Júnior
authors.affiliation: Laboratory of Genetics, Butantan Institute, Sao Paulo, SP, Brazil, ; Morphology and Genetics Department, Universidade Federal de Sao Paulo, SP, Brazil.
authors.forename: Diana Aparecida Dias
authors.initials: DA
authors.lastname: Câmara
authors.affiliation: Laboratory of Genetics, Butantan Institute, Sao Paulo, SP, Brazil.
authors.forename: André Santos
authors.initials: AS
authors.lastname: Costa
authors.affiliation: Laboratory of Genetics and Molecular Hematology (LIM31), University of Sao Paulo School of Medicine, Sao Paulo, SP, Brazil.
authors.forename: Jorge Luis Maria
authors.initials: JL
authors.lastname: Ruiz
authors.affiliation: Laboratory of Genetics and Molecular Hematology (LIM31), University of Sao Paulo School of Medicine, Sao Paulo, SP, Brazil.
authors.forename: Débora
authors.initials: D
authors.lastname: Levy
authors.affiliation: Departament of Immunology, Laboratory of Tumor Immunology, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Ricardo Alexandre
authors.initials: RA
authors.lastname: Azevedo
authors.affiliation: Biochemistry and Biophysics Laboratory, Butantan Institute, Sao Paulo, SP, Brazil.
authors.forename: Kerly Fernanda Mesquita
authors.initials: KF
authors.lastname: Pasqualoto
authors.affiliation: Laboratory of Genetics, Butantan Institute, Sao Paulo, SP, Brazil.
authors.forename: Camila Fávero
authors.initials: CF
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Genetics, Butantan Institute, Sao Paulo, SP, Brazil.
authors.forename: Thatiana Corrêa
authors.initials: TC
authors.lastname: de Melo
authors.affiliation: Programa de Pós-graduação em Ciências da Saúde, Faculdade de Ciências Médicas, Universidade de Pernambuco (UPE).
authors.forename: Nara Diniz Soares
authors.initials: ND
authors.lastname: Pessoa
authors.affiliation: Camilo Castelo Branco University, Department of Biomedical Instrumentation, Biomedical Engineering Center, Sao Jose dos Campos, Sao Paulo, SP, Brazil.
authors.forename: Pâmela Maria Moreira
authors.initials: PM
authors.lastname: Fonseca
authors.affiliation: Laboratory of Genetics, Butantan Institute, Sao Paulo, SP, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pereira
authors.affiliation: Laboratory of Genetics, Butantan Institute, Sao Paulo, SP, Brazil.
authors.forename: Rodrigo Pinheiro
authors.initials: RP
authors.lastname: Araldi
authors.affiliation: Departament of Immunology, Laboratory of Tumor Immunology, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Adilson Kleber
authors.initials: AK
authors.lastname: Ferreira
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D020552:Comet Assay; D005054:Eugenol / Q000494:pharmacology*; D005260:Female; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D009153:Mutagens / Q000633:toxicity*; D009369:Neoplasms / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009153:Mutagens; D018809:Proliferating Cell Nuclear Antigen; D017382:Reactive Oxygen Species; D005054:Eugenol
keywords: Apoptosis; Cancer; Cell-cycle; Eugenol; Mitochondria potential