Effects of polyphenols: Resveratrol and its natural analogues and tannic acid on DNA oxidative damage and apoptosis in human neutrophils

Our earlier studies (1,2) showed that tannic acid and naturally occurring stilbenes resveratrol and its analogue pterostilbene, the common ingredients of berries fruits, are involved in the key events of the initiation and promotion stages of carcinogenesis. The latter included the inhibition of transcription factors responsible for the inflammatory response. The aim of this study was to evaluate the effect of these compounds on DNA oxidative damage and apoptosis in human polymorphonuclear neutrophils (PMN). In order to induce oxidative burst PMN were stimulated with 12Otetradecanoylphorbol13acetate. Treatment of PMN with the tested polyphenols at the concentration range which did not show cytotoxicity resulted in the reduced production of reactive oxygen species and subsequently DNA oxidative damage assessed by Single Cell Gel Electrophoresis (comet assay). Tannic acid caused the 50% decrease in DNA oxidative decomposition at the concentration as low as 1µmol. Resveratrol caused a similar effect at a concentration 100 times higher. All tested polyphenols induced apoptosis by increasing the activity of procaspase3, phosphatidylserine translocation and loss of mitochondrial membrane potential. The highest proapoptotic activity was demonstrated by 3'5,4'trimethoxystilbene and tannic acid. This effect however was dependent on the dose. At the higher concentrations (50µmol) an antiapoptotic effect was observed. Collectively ROS production in activated PMN seems to influence their lifespan and can be modulated by stilbenes and phenolic acids. Such activity might be useful in adjuvant therapy of inflammatory diseases.

References: 1. Cichocki, M. et al. (2008) Mol.Nutr.Food Res. 52: S62-S70.

2. Cichocki, M. et al. (2010) Toxicology 268: 118–124.