Inhibition of DMBA-induced Oral Squamous Cells Carcinoma Growth by Brazilian Red Propolis in Rodent Model

Basic Clin Pharmacol Toxicol. 2015 Aug;117(2):85-95. doi: 10.1111/bcpt.12374. Epub 2015 Feb 25.

Abstract

We investigated the effect of oral administration of hydroalcoholic extract of Brazilian red propolis (HERP) on DMBA-induced oral squamous cell carcinomas (OSCC) in rodents. The chemical components of the HERP were assessed by high-performance liquid chromatography (HPLC). Carcinogenesis was topically induced in the lower lip of 25 rats using 9,10-dimethyl-1,2-benzanthracene (DMBA); the tumour was treated with saline (TUM1) and Tween 80 (TUM2) as well as HERP at 10, 50 and 100 mg/kg (HERP10, HERP50 and HERP100, respectively) for 20 weeks. Topical application of saline and oral administration of 100 mg/kg HERP was used in five rats as a control group (CTR). After 26 weeks, the histological malignancy grading and immunohistochemical expression of Ki-67 and p16(INK4A) were assessed in the tumours/tissue samples. The compounds identified were propyl gallate, daidzein, catechin, epicatechin, formononetin and biochanin A. Formononetin, daidzein and biochanin A showed concentration of 23.29, 0.38 and 0.67 mg/g of HERP, respectively. HERP at doses of 50 and 100 mg/kg inhibited 40% of OSCC growth and promoted a 3-week delay in development of clinically detectable tumours. Epithelial dysplasia was observed in all samples with no clinical tumour, except in CTR. No significant difference in the immunoexpression of Ki-67 and p16(INK4A) was observed between HERP-treated and saline/Tween 80-treated groups (p > 0.05). Our results suggest that HERP exerts chemopreventive activity on the progression of DMBA-induced epithelial dysplasia to OSCC in an experimental model of labial carcinogenesis; however, this effect is not associated with Ki-67 and p16(INK4A) immunoexpression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity
  • Administration, Oral
  • Animals
  • Brazil
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / prevention & control*
  • Chemoprevention / methods
  • Chromatography, High Pressure Liquid
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / prevention & control*
  • Propolis / administration & dosage
  • Propolis / chemistry
  • Propolis / pharmacology*
  • Rats

Substances

  • 9,10-Dimethyl-1,2-benzanthracene
  • Propolis