A8.20 A novel resveratrol prodrug: anti-proliferative and pro-apoptotic effects in human T-cells

Background and objectives

Resveratrol is a naturally occuring polyphenol produced in many plants (red grapes, raspberries, blueberries, etc.). The positive health effects of resveratrol are due its potent anti-inflammatory, anti-oxidant and anti-proliferative activities in many types of cancer cells. Due to the fact that resveratrol is sensitive to oxygen and is almost insoluble in water, its therapeutic application is very limited. Therefore, work is going on designing resveratrol analogues to improve the solubility and bioavailability of the natural resveratrol. Recently, we designed and synthesised a resveratrol prodrug (FEHH4–1) which is only active within the cells. Through esterification of all three phenolic groups, stability as well as lipophilicity of the natural resveratrol could be improved. In the present study, we compared the effects of resveratrol with FEHH4–1 on Jurkat T- cells.

Material and methods

Jurkat T- cells were stimulated with PMA/PHA in the absence or presence of different concentrations of resveratrol or FEHH4–1. Modulation in IL-2 promoter activity was monitored by a IL-2 luciferase reporter assay. IL-2 release was quantified by enzyme-linked immunosorbent assay (ELISA). The effects of resveratrol and FEHH4–1 on cell proliferation and apoptosis were evaluated by XTT assay, Annexin-V/7-AAD staining and Western blot.

Results

Both resveratrol and FEHH4–1 effectively attenuated IL-2 promoter activity and IL-2 expression in stimulated Jurkat T- cells. At a concentration of 25 µM, resveratrol blocked IL-2 production at about 50%, FEHH4–1, however, at about 80%. Additionally, we observed that FEHH4–1 reduced cell proliferation and induced apoptotic cell death at significantly lower concentrations than resveratrol.

Conclusion

The resveratrol prodrug FEHH4–1 significantly amplified the beneficial effects of resveratrol in Jurkat T- cells. In comparison to resveratrol, FEHH4–1 enhanced downregulation of IL-2 production, and decreased proliferation rate in Jurkat T- cells. These data indicate that FEHH4–1 could be a substitute for the natural resveratrol in the future.