Chemopreventive activity of apple extract following medium-term oral carcinogenesis assay induced by 4-nitroquinoline-1-oxide

Flávia Andressa Pidone Ribeiro; Carolina Foot Gomes de Moura; Andrea Pitelli Boiago Gollucke; Mônica Siqueira Ferreira; Rodrigo Ramos Catharino; Odair Aguiar Jr; Regina Celia Spadari; Luis Fernando Barbisan; Daniel Araki Ribeiro

doi:10.1016/j.archoralbio.2014.04.013

Chemopreventive activity of apple extract following medium-term oral carcinogenesis assay induced by 4-nitroquinoline-1-oxide

Arch Oral Biol. 2014 Aug;59(8):815-21. doi: 10.1016/j.archoralbio.2014.04.013. Epub 2014 Apr 27.

Authors

Flávia Andressa Pidone Ribeiro¹, Carolina Foot Gomes de Moura², Andrea Pitelli Boiago Gollucke³, Mônica Siqueira Ferreira⁴, Rodrigo Ramos Catharino⁴, Odair Aguiar Jr¹, Regina Celia Spadari¹, Luis Fernando Barbisan⁵, Daniel Araki Ribeiro⁶

Affiliations

¹ Department of Biosciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil.
² Department of Pathology, Federal University of Sao Paulo, UNIFESP, SP, Brazil.
³ Hexalab, Catholic Santos University, Santos, SP, Brazil.
⁴ INNOVARE Biomarkers Laboratory, Medicine and Experimental Surgery Nucleus, University of Campinas, Campinas, SP, Brazil.
⁵ Department of Morphology, Institute of Biosciences, Paulista State University, Botucatu, SP, Brazil.
⁶ Department of Biosciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil; Hexalab, Catholic Santos University, Santos, SP, Brazil. Electronic address: daribeiro@unifesp.br.

PMID: 24863658
DOI: 10.1016/j.archoralbio.2014.04.013

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.

Conclusion: 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.

Keywords: 4-Nitroquinoline-1-oxide; Apoptosis; Apple extract; Inflammation; Oral cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

4-Nitroquinoline-1-oxide
Animals
Antineoplastic Agents / pharmacology*
Apoptosis
Carcinogenesis / drug effects
Carcinoma, Squamous Cell / chemically induced
Carcinoma, Squamous Cell / drug therapy*
Free Radical Scavengers / pharmacology*
Male
Malus*
Mouth Neoplasms / chemically induced
Mouth Neoplasms / drug therapy*
Plant Extracts / pharmacology*
Polymerase Chain Reaction / methods
RNA / analysis
Rats
Rats, Wistar

Substances

Antineoplastic Agents
Free Radical Scavengers
Plant Extracts
4-Nitroquinoline-1-oxide
RNA