Resveratrol induces Fas signalling-independent apoptosis in THP-1 human monocytic leukaemia cells

Rosveratrol, a natural product present in wine, has recently been shown to inhibit the growth of a number of cancer cell lines in vitro, In the curren t study, we have demonstrated that resveratrol inhibits the growth of THP-1 human monocytic leukaemia cells in a dose-dependent manner with a median e ffective dose of 12 mu M. It did not induce differentiation of THP-1 cells and had no toxic effect on THP-1 cells that had been induced to differentia te into monocytcs/macrophagcs by phorbol myristate acetate, A significant f raction of resveratrol-treated cells underwent apoptosis as judged by flow cytometric analysis of DNA content, DNA fragmentation and caspase-specific cleavage of poly(ADP-ribosyl) polymerase. Resveratrol treatment had no effe ct on the expression of Fas receptor or Fas ligand (FasL) in THP-1 cells, n or did it induce clustering of Fas receptors, In addition, THP-1 cells were resistant to activating anti-Fas antibody, and neutralizing anti-Fas and/o r anti-FasL antibodies had no protective effect against resveratrol-induced inhibition of THP-1 cell growth. The effect of resveratrol on THP-1 cells was reversible after its removal from the culture medium. These results sug gest that (1) resveratrol inhibits the growth of THP-1 cells, at least in p art, by inducing apoptosis, (2) resveratrol-induced apoptosis of THP-1 cell s is independent of the Fas/FasL signalling pathway and (3) resveratrol doe s not induce differentation of THP-1 cells and has no toxic effect on diffe rentiated THP-1 cells. Thus, resveratrol may be a potential chemotherapeuti c agent for the control of acute monocytic leukaemia.