Effects of resveratrol on proliferation and apoptosis in rat ovarian theca-interstitial cells

• Published in: Molecular human reproduction 2010-04, Vol.16 (4), p.251-259
• Main Authors: Wong, Donna H., Villanueva, Jesus A., Cress, Amanda B., Duleba, Antoni J.
• Format: Article
• Language: English
• Subjects: Animals; Anticarcinogenic Agents - pharmacology; apoptosis; Apoptosis - drug effects; Biological and medical sciences; Caspases - metabolism; Cell Proliferation - drug effects; Cells, Cultured; DNA Fragmentation - drug effects; Embryology: invertebrates and vertebrates. Teratology; Female; Fundamental and applied biological sciences. Psychology; In Situ Nick-End Labeling; insulin; ovarian theca-interstitial cells; proliferation; Rats; resveratrol; Stilbenes - pharmacology; Theca Cells - cytology; Theca Cells - drug effects
• ISSN: 1360-9947; 1460-2407
• DOI: 10.1093/molehr/gaq002

Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction and associated with ovarian theca-interstitial (T-I) cell hyperplasia, hyperinsulinemia, systemic inflammation and oxidative stress. This in vitro study tested whether rat T-I cell growth with or without insulin can be altered by resveratrol, a natural polyphenol with anti-carcinogenic, anti-inflammatory, anti-proliferative and antioxidant properties. Rat T-I cells were cultured with and without resveratrol and/or insulin, and the effects on DNA synthesis, number of viable cells and markers of apoptosis were evaluated. Resveratrol alone induced a potent concentration-dependent inhibition of cell growth by inhibiting DNA synthesis, decreasing the number of viable cells and increasing the activity of executioner caspases 3 and 7; these effects of resveratrol counteracted the pro-proliferative and anti-apoptotic effects of insulin. Immunofluorescence analysis of cells incubated with resveratrol showed concentration- and time-dependent morphological changes consistent with apoptosis. The present findings indicate that resveratrol promotes apoptosis to reduce rat T-I cell growth in vitro as well as inhibiting insulin-induced rat T-I cell growth. This suggests a possibility that resveratrol and/or mechanisms mediating its effect may be relevant to the development of novel treatments for PCOS, which is characterized by both excessive ovarian mesenchyma growth and hyperinsulinemia.