Effect of resveratrol and its hydroxylated analogues on proliferation and apoptosis oftwo cervix cancer derived cancer cell lines. The role of mitochondrial superoxidedismutase

The naturally occurring polyphenol resveratrol (3,4',5-trihydroxy-stilbene, 3,4',5-THS, RES) has been shown as a chemopreventive and proapototic agent. Resveratrol is extensively metabolized by CYP450 enzymes. The monohy- droxylation of resveratrol is catalyzed by CYP1B1 to form 3,3',4',5-THS (piceatannol), a metabolite with higher antican- cer activity and stronger antioxidant properties. It was hypothesized that RES analogues (HHRAs) possessing more than 3 hydroxyl groups may act stronger against cancer cells than RES due to reactive oxygen species formed in redox-cycling reactions. In order to investigate a structure-activity relationship between pro/antioxidant properties and cytotoxicity, the HHRAs with at least 2 phenolic groups in neighborhood- 3,4,4',5-HS and 3,3',4,4',5,5'-HS were synthesized. In the present study we tested this hypothesis in a cell culture model using HeLa and C33A cancer cell lines. The results of our experi- ments support a hypothesis that MnSOD overexpressing HeLa cells are much more resistant to superoxide generating HHRAs than C33A cells.