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Resveratrol induces Fas signalling‐independent apoptosis in THP‐1 human monocytic leukaemia cells
Author(s) -
Tsan MinFu,
White Julie E.,
Maheshwari Jewraj G.,
Bremner Theodore A.,
Sacco Joseph
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.01980.x
Subject(s) - resveratrol , thp1 cell line , apoptosis , dna fragmentation , microbiology and biotechnology , cell culture , fas ligand , chemistry , biology , programmed cell death , biochemistry , genetics
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 μ m . 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.