Cytotoxicity mechanisms in melanoma cells and UPLC-QTOF/MS2 chemical characterization of two Brazilian stingless bee propolis: Uncommon presence of piperidinic alkaloids

J Pharm Biomed Anal. 2018 Feb 5:149:502-511. doi: 10.1016/j.jpba.2017.11.038. Epub 2017 Nov 12.

Abstract

The present study characterized propolis extracts produced by Scaptotrigona bipunctata (Tubuna) and Melipona quadrifasciata (Mandaçaia) by LC-MS/MS; their cytotoxicity as well as the mechanism of action in a melanoma cellular model were also assessed. The chemical characterization performed by UPLC-ESI-QTOF/MS2 analysis revealed uncommon presence of piperidinic alkaloids in Tubuna's propolis extract together with C-glycopyranoside flavonoids. Mandaçaia's propolis collected in the same area rather presented terpenoids and flavonoids. Regarding the mechanism of cytotoxicity, propolis extracts increased the accumulation of reactive oxygen species (ROS), reduced the potential of mitochondrial membrane, induced a decrease in the proteins Bcl-2 and AKT-3 levels, and decreased melanoma cells' migration and invasion. Both propolis extracts induced apoptosis while only Mandaçaia's propolis extract induced cell cycle arrest in G2/M.

Keywords: Chemical composition; Cytotoxicity; Melanoma cells; Melipona quadrifasciata; Propolis; Scaptotrigona bipunctata.

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / pharmacology
  • Animals
  • Apoptosis / drug effects*
  • Bees / physiology
  • Brazil
  • Cell Line, Tumor
  • Cell Movement
  • Chromatography, High Pressure Liquid / instrumentation
  • Chromatography, High Pressure Liquid / methods
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Melanoma / drug therapy*
  • Membrane Potential, Mitochondrial / drug effects
  • Piperidines / chemistry
  • Piperidines / pharmacology
  • Propolis / chemistry
  • Propolis / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Skin Neoplasms / drug therapy*
  • Spectrometry, Mass, Electrospray Ionization / instrumentation
  • Spectrometry, Mass, Electrospray Ionization / methods
  • Tandem Mass Spectrometry / instrumentation
  • Tandem Mass Spectrometry / methods

Substances

  • Alkaloids
  • Piperidines
  • Reactive Oxygen Species
  • Propolis