Resveratrol induces Fas signalling-independent apoptosis in THP-1 human monocytic leukaemia cells.
Resveratrol, 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 current study, we have demonstrated that resveratrol inhibits the growth of THP-1 human monocytic leukaemia cells in a dose-dependent manner with a median effective dose of 12 microM. It did not induce differentiation of THP-1 cells and had no toxic effect on THP-1 cells that had been induced to differentiate into monocytes/macrophages by phorbol myristate acetate. A significant fraction 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 effect on the expression of Fas receptor or Fas ligand (FasL) in THP-1 cells, nor did it induce clustering of Fas receptors. In addition, THP-1 cells were resistant to activating anti-Fas antibody, and neutralizing anti-Fas and/or 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 suggest that (1) resveratrol inhibits the growth of THP-1 cells, at least in part, by inducing apoptosis, (2) resveratrol-induced apoptosis of THP-1 cells is independent of the Fas/FasL signalling pathway and (3) resveratrol does not induce differentation of THP-1 cells and has no toxic effect on differentiated THP-1 cells. Thus, resveratrol may be a potential chemotherapeutic agent for the control of acute monocytic leukaemia.
Tsan
M F
MF
Research and Medical Services, Stratton VA Medical Center, Albany, NY 12208, USA.
White
J E
JE
Maheshwari
J G
JG
Bremner
T A
TA
Sacco
J
J
D000704:Analysis of Variance; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells / Q000187:drug effects; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000032:analysis; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D019014:fas Receptor / Q000032:analysis
D000972:Antineoplastic Agents, Phytogenic; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D013267:Stilbenes; D019014:fas Receptor; D000077185:Resveratrol