Chemoprevention by Quercetin of Oral Squamous Cell Carcinoma by Suppression of the NF-κB Signaling Pathway in DMBA-treated Hamsters

Anticancer Res. 2017 Aug;37(8):4041-4049. doi: 10.21873/anticanres.11789.

Abstract

Background/aim: The aim of this study was to investigate the effects of the flavonoid quercetin on chemoprevention of oral squamous cell carcinoma (OSCC). The study involved molecular signaling pathways in 7,12-dimethylbenz(a) anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis.

Materials and methods: DMBA (0.5%) was painted at the right buccal pouches of hamsters for 14 weeks to induce carcinoma. DMBA-treated hamsters received simultaneous doses of quercetin. Animals without DMBA induction were used as normal controls. The incidence of OSCC and the severity of pre-malignant lesions were determined histologically. Apoptosis in the pouch tissue was determined by TUNEL staining. The mRNA and protein expression of NF-κB p50 and p65, as well as Bcl-2 and Bax genes were analyzed using RT-PCR and Western blotting, respectively.

Results: Quercetin, at various doses, significantly reduced OSCC incidence and severity of hyperplasia and dysplasia compared to the DMBA-induction-only group (p<0.01). Apoptosis was induced by quercetin treatment compared to the DMBA-induction-only group (p<0.01). mRNA and protein expression of NF-κB p50, p65 as well as Bcl-2 genes were significantly suppressed by quercetin at high doses compared to DMBA induction only (p<0.05). However, mRNA and protein expression of the Bax gene was increased by quercetin treatment at medium and high doses, compared to the DMBA-induction-only group (p<0.05). Quercetin significantly reduced body-weight loss compared to the DMBA-induction-only group (p<0.05).

Conclusion: Quercetin reduced tumor incidence and induced apoptosis through modulation of NF-κB signaling and its target genes Bcl-2 and Bax in the DMBA-induced carcigenesis hamster model, suggesting the potential of quercetin as a candidate for OSCC chemoprevention.

Keywords: 7,12-dimethylbenz(a)anthracene (DMBA); NF-κB; chemoprevention; hamster; oral squamous cell carcinoma; quercetin.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity
  • Animals
  • Apoptosis / drug effects
  • Carcinogenesis / drug effects
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Cricetinae
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mouth Neoplasms / chemically induced
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / pathology
  • NF-kappa B / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Quercetin / administration & dosage*
  • Signal Transduction / drug effects
  • bcl-2-Associated X Protein / biosynthesis
  • bcl-2-Associated X Protein / genetics

Substances

  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • 9,10-Dimethyl-1,2-benzanthracene
  • Quercetin