title: Molecular targets of the natural antioxidant pterostilbene: effect on protein kinase C, caspase-3 and apoptosis in human neutrophils in vitro.
abstract: OBJECTIVE
  Pterostilbene, a naturally occurring phenolic derivative, exhibits various pharmacological effects, e.g. anti-cancerous, antioxidant, anti-inflammatory and anti-diabetic. Based on our previous study, we assessed the cellular and molecular effects of pterostilbene on human neutrophils and in cell free systems. Experimental and theoretical molecular descriptors of stilbene derivatives were also determined.
  
  
  METHODS
  We assessed the antioxidant properties of pterostilbene using cell free system and computational methods. The effect of pterostilbene on protein kinase C activation/phosphorylation was detected by special anti-phospho protein kinase C antibodies. Membrane associated changes determining the life span of neutrophils and human recombinant caspase-3 assay were examined.
  
  
  RESULTS
  Pterostilbene possessed comparable antioxidant properties as resveratrol in cell free system. Computational methods were used to establish the molecular characteristics of stilbene derivatives. The values of electronic parameters suggest a slight enhancement of electron donor properties of pterostilbene compared to resveratrol. Phosphorylation and thus activation of protein kinase C alpha/beta II in activated neutrophils was not decreased by pterostilbene. Pterostilbene in concentrations of 10-100 μM was found to inhibit the activity of human caspase-3 purified enzyme and did not influence cell viability significantly.
  
  
  CONCLUSIONS
  Pterostilbene, an analog of resveratrol, was identified as a good natural antioxidant compound. However, reducing the oxidative burst of human neutrophils during their activation in vitro with pterostilbene does not include protein kinase C phosphorylation pathway. Pterostilbene showed dose dependent activation/inhibition of caspase-3 enzyme activity.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovakia. tomas.perecko@savba.sk
authors.forename: Tomas
authors.initials: T
authors.lastname: Perecko
authors.forename: Katarina
authors.initials: K
authors.lastname: Drabikova
authors.forename: Lucia
authors.initials: L
authors.lastname: Rackova
authors.forename: Milan
authors.initials: M
authors.lastname: Ciz
authors.forename: Martina
authors.initials: M
authors.lastname: Podborska
authors.forename: Antonin
authors.initials: A
authors.lastname: Lojek
authors.forename: Juraj
authors.initials: J
authors.lastname: Harmatha
authors.forename: Jan
authors.initials: J
authors.lastname: Smidrkal
authors.forename: Radomir
authors.initials: R
authors.lastname: Nosal
authors.forename: Viera
authors.initials: V
authors.lastname: Jancinova
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D013267:Stilbenes; C107773:pterostilbene; D011493:Protein Kinase C; D053148:Caspase 3; D000077185:Resveratrol