Biological effects on granulosa cells of hydroxylated and methylated resveratrol analogues.
Several resveratrol analogues have been designed to improve bioactivity: among these polymethoxystilbenes appear to be particularly promising. The present study was set up to investigate the biological functions of polymethoxystilbenes 2 and 3, recently found in our lab as antiangiogenic agents, on a well-defined swine granulosa cell model. Proliferative activity and effects on steroidogenesis were evaluated, as well as the effect on granulosa cell vascular endothelial growth factor (VEGF) production, since these cells in basic conditions synthesize the main proangiogenic peptide. Moreover, we considered the effect of these two resveratrol analogues on granulosa cell redox status. Analogue 3 inhibited granulosa cell growth, while it stimulated steroidogenesis. A similar effect was displayed by 2 on estradiol 17beta production and cell proliferation at the highest concentration tested. On the other hand, at the same dosage 2 decreased progesterone levels. Both analogues inhibited VEGF output. Granulosa cell redox status was unaffected by resveratrol analogue 2 while the highest concentration of 3 stimulated free radicals generation and scavenging enzyme activities. The overall results indicate that analogue 3 is the more powerful compound, thus suggesting that a slight modification in the structure markedly increases effectiveness. These data could be useful to develop more active resveratrol analogues for therapeutic use.
Dipartimento di Produzioni Animali, Biotecnologie Veterinarie, Qualità e Sicurezza degli Alimenti-Sezione di Fisiologia, Parma, Italy. basini@unipr.it
Giuseppina
G
Basini
Corrado
C
Tringali
Laura
L
Baioni
Simona
S
Bussolati
Carmela
C
Spatafora
Francesca
F
Grasselli
D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D006900:Hydroxylation; D008745:Methylation; D009994:Osmolar Concentration; D006080:Ovarian Follicle / Q000166:cytology; D010088:Oxidoreductases / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D034421:Sus scrofa; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D013267:Stilbenes; D042442:Vascular Endothelial Growth Factors; D013481:Superoxides; D011374:Progesterone; D004958:Estradiol; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D000077185:Resveratrol