title: Chemopreventive activity of apple extract following medium-term oral carcinogenesis assay induced by 4-nitroquinoline-1-oxide.
abstract: OBJECTIVE
  The aim of this study was to evaluate the chemopreventive activity of an apple extract following medium-term oral carcinogenesis assay induced by 4-nitroquinoline-1-oxide (4NQO).
  
  
  METHODS
  A total of 30 male Wistar rats were distributed into five groups as follows (n=6 per group): Group 1, negative control group (non-treated group); Group 2, received 4NQO during 8 weeks in drinking water and treated with apple extract at 1% by gavage between the first and fourth weeks daily (initiation phase); Group 3, received 4NQO for 8 weeks in drinking water and treated with apple extract by gavage at 1% between the fifth and eighth weeks daily (promotion phase); Group 4, received apple extract at 1% by gavage for 8 consecutive weeks only; and Group 5, received 4NQO for 8 weeks in drinking water daily.
  
  
  RESULTS
  Histopathological analysis revealed decreased hyperplasic lesions in Group 2 when compared with Group 5. Likewise, decreased dysplastic lesions in Group 3 were observed when compared with Group 5. In Groups 2 and 3, decreased COX-2 and TNF-alpha gene expressions were observed when compared with Group 5. Cytochrome c and caspase 3 levels increased in Groups 2 and 3 when compared with Group 5.
  
  
  CONCLUSIONS
  In conclusion, our results demonstrate that apple extract suppresses rat tongue carcinogenesis as a result of anti-inflammatory activity and apoptosis through the intrinsic mitochondrial pathway.
authors.affiliation: Department of Biosciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil.
authors.forename: Flávia Andressa Pidone
authors.initials: FA
authors.lastname: Ribeiro
authors.affiliation: Department of Pathology, Federal University of Sao Paulo, UNIFESP, SP, Brazil.
authors.forename: Carolina Foot Gomes
authors.initials: CF
authors.lastname: de Moura
authors.affiliation: Hexalab, Catholic Santos University, Santos, SP, Brazil.
authors.forename: Andrea Pitelli Boiago
authors.initials: AP
authors.lastname: Gollucke
authors.affiliation: INNOVARE Biomarkers Laboratory, Medicine and Experimental Surgery Nucleus, University of Campinas, Campinas, SP, Brazil.
authors.forename: Mônica Siqueira
authors.initials: MS
authors.lastname: Ferreira
authors.affiliation: INNOVARE Biomarkers Laboratory, Medicine and Experimental Surgery Nucleus, University of Campinas, Campinas, SP, Brazil.
authors.forename: Rodrigo Ramos
authors.initials: RR
authors.lastname: Catharino
authors.affiliation: Department of Biosciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil.
authors.forename: Odair
authors.initials: O
authors.lastname: Aguiar
authors.affiliation: Department of Biosciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil.
authors.forename: Regina Celia
authors.initials: RC
authors.lastname: Spadari
authors.affiliation: Department of Morphology, Institute of Biosciences, Paulista State University, Botucatu, SP, Brazil.
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Barbisan
authors.affiliation: Department of Biosciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil; Hexalab, Catholic Santos University, Santos, SP, Brazil. Electronic address: daribeiro@unifesp.br.
authors.forename: Daniel Araki
authors.initials: DA
authors.lastname: Ribeiro
mesh_terms: D015112:4-Nitroquinoline-1-oxide; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D063646:Carcinogenesis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000188:drug therapy*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008297:Male; D027845:Malus; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D010936:Plant Extracts / Q000494:pharmacology*; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D010936:Plant Extracts; D015112:4-Nitroquinoline-1-oxide; D012313:RNA
keywords: 4-Nitroquinoline-1-oxide; Apoptosis; Apple extract; Inflammation; Oral cancer