Effect of Resveratrol and its Hydroxylated Analogues on Proliferation and Apoptosis of Two Cervix Cancer Derived Cancer Cell Lines. The Role of Mitochondrial Superoxide Dismutase

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 monohydroxylation of resveratrol is catalyzed by CYP1B1 to form 3,3',4',5-THS (piceatannol), a metabolite with higher anticancer 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 neighborhood3,4,4',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 experiments support a hypothesis that MnSOD overexpressing HeLa cells are much more resistant to superoxide generating HHRAs than C33A cells.