FADD-dependent apoptosis induction in Jurkat leukemia T-cells by the resveratrol analogue, 3,4,5-trihydroxy-trans-stilbene

The plant-produced compound, resveratrol (3,5,4′-trihydroxy-trans-stilbene, 3,4,5-THS), induces apoptosis in various human leukemia cell types in vitro, and thus appears to be a promising anti-leukemia agent. In this study, we observed that treatment of resveratrol-resistant Jurkat cells with the resveratrol analogue, 3,4,5-trihydroxy-trans-stilbene (3,4,5-THS), rapidly induced extensive apoptosis, indicating that the apoptotic activity of the analogue differed from that of the parental compound resveratrol. Indeed, we found that treatment of Jurkat cells with 3,4,5-THS, unlike treatment with resveratrol, induced activation of caspase-8 and apoptosis by a Fas-associated death domain (FADD) protein-dependent mechanism without involving the known death ligands CD95 ligand (CD95L), tumor necrosis factor α (TNFα) and TNF-related apoptosis-inducing ligand (TRAIL). Therefore, 3,4,5-THS induced activation of a FADD-dependent apoptotic mechanism that was unresponsive to the parental compound resveratrol. Therefore, the ability of 3,4,5-THS, but not resveratrol, to induce apoptosis demonstrates a structure-associated apoptotic activity of the resveratrol analogue.