Angiogenesis inhibition by green propolis and the angiogenic effect of L-lysine on bladder cancer in rats

Acta Cir Bras. 2012 Aug;27(8):529-36. doi: 10.1590/s0102-86502012000800003.


Purpose: To determine the effects of water-soluble derivative of green propolis in bladder cancer angiogenesis in rats given N-butyl-(-4-hydroxybutyl) nitrosamine (BBN).

Methods: Nine groups were established, where six of them (Groups 1 to 6), the animals received 0.05% BBN in their drinking water for 14 weeks. From the 32nd to the 40th week, Groups 1, 2, 3 and 4 were treated respectively with water, L-lysine (300 mg/kg/day), celecoxib (30 mg/kg/day) and propolis (300 mg/kg/day). Groups 5 and 6 were given propolis and L-lysine from the 1st to the 40th week (150 mg/kg/day). Microvascular density was determined by histological sections stained for the marker CD-31 and analyzed with specific software.

Results: The microvascular density in bladder carcinomas was lower (p<0.01) in rats receiving propolis than in controls given carcinogen only. On the other hand, the microvascular density of tumors in rats receiving carcinogen and L-lysine for 40 weeks from the beginning of carcinogen treatment was significantly higher (p<0.01) than in the corresponding controls.

Conclusion: Water-soluble derivative of propolis inhibits angiogenesis in BBN-induced rat bladder cancer, while L-lysine treatment stimulates angiogenesis if initiated concurrently with BBN.

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Butylhydroxybutylnitrosamine / therapeutic use*
  • Carcinoma / drug therapy*
  • Carcinoma / pathology
  • Disease Models, Animal
  • Female
  • Lysine / therapeutic use*
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Plant Extracts / therapeutic use
  • Propolis / therapeutic use*
  • Rats
  • Rats, Wistar
  • Time Factors
  • Treatment Outcome
  • Urinary Bladder Neoplasms / blood supply
  • Urinary Bladder Neoplasms / drug therapy*
  • Water / chemistry


  • Angiogenesis Inhibitors
  • Plant Extracts
  • Water
  • Butylhydroxybutylnitrosamine
  • Propolis
  • Lysine