BACKGROUND: This study was conducted to determine the effects of resveratrol on prostate cancer cell viability through apoptosis induction and the significance of the three hydroxyl groups on resveratrol to the measured effect. METHODS: Hormone-sensitive LNCaP cells and hormone-insensitive DU 145 cells were treated with resveratrol, tri-methoxy-resveratrol, or diethylstilbestrol (DES; the positive control for toxicity and apoptosis). Cell viability was determined by using an MTS assay. Apoptosis was determined by the appearance of apoptotic morphology, annexin V-FITC-positive intact cells, and caspase activation. RESULTS: Resveratrol and DES decreased viability in LNCaP cells, but only resveratrol-treated cells expressed apoptotic morphology, annexin V-FITC-positive cells, and caspase activation. Tri-methoxy-resveratrol had no effect on DU 145 cell-viability and was less toxic to LNCaP cells than resveratrol. CONCLUSION: Resveratrol was toxic to cells regardless of whether the cells were hormone-responsive or -unresponsive. This finding suggests that the cell's hormone responsive status is not an important determinant of the response to resveratrol. Furthermore, the hydroxyl-groups on resveratrol are required for cell toxicity. Finally resveratrol but not DES induced caspase-mediated apoptosis. Morris GZ, Williams RL, Elliott MS, Beebe SJ. Prostate 2002 Sep 1;52(4):319-29.