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

Abstract

Summary. 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 mm. 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.

Resveratrol induces colon tumor cell apoptosis independently of p53 and precede by epithelial differentiation, mitochondrial proliferation and membrane potential collapse

“…24 Still others have described that resveratrol causes apoptosis independently of Fas signaling. 20 In agreement with the findings showing that resveratrol-induced apoptosis is not dependent on Fas/FasL, we present here data indicating that HCT116 cells die a "mitochondrion type" and not a "death receptor type", of apoptosis.…”

“…15 We report here that, in contrast to the results obtained with mouse embryo fibroblasts, resveratrol induces apoptosis in human microsatellite-unstable colon carcinoma cell line HCT116 regardless of p53 status and at concentrations comparable to those found in wine and grapes. As has been shown for THP-1 human monocytic leukemia cells, 20 the effect was reversible after removal of the drug from the culture; nevertheless, the continuous presence of resveratrol for 120 hr resulted in complete eradication of the culture. Remarkably, p53 appears to have a limited protective effect against apoptosis at low resveratrol concentrations.…”

“…22 Furthermore, mouse and human leukemic cells selectively undergo apoptosis under resveratrol, while hematopoietic progenitor cells and differentiated cells are largely resistant. 20,23 However, different cell types and even the same cell lines have produced conflicting results with regard to the effects of resveratrol. In the human HL60 promyelocytic leukemia cell line, the drug has been variably reported to induce apoptosis, 24 differentiation 2 and differentiation with S/G 2 arrest without apoptosis.…”

Sirtuin-1 (SIRT1) Is Required for Promoting Chondrogenic Differentiation of Mesenchymal Stem Cells

“…Several reports have demonstrated that resveratrol has anti-inflammatory, antioxidant, and antitumor activity in cancer cell lines derived from human and animal tumors (22)(23)(24). One of the most important and functional novel molecular targets of resveratrol is sirtuin-1 (SIRT1), a member of the sirtuin family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, which is found to be an anti-aging gene (25,26).…”

New insights on the anticancer properties of dietary polyphenols

“…Nevertheless, some phenolic compounds such as curcumin seem to induce apoptosis only in immortalized (malignant) cells: immortalized mouse embryo fibroblasts NIH 3T3, erB2, mouse Sarcoma 180, human colon cancer cell HT29, human kidney cancer cell 293, and human hepatocellular carcinoma HepG2 cells 54 (see also Table I). Moreover, other polyphenols such as resveratrol trigger apoptosis in carcinoma cells: Hep-G2 cells, 55 acute lymphoblastic leukemia cells, 56 THP-1 human monocytic leukemia cells 57 and oral cancer cell lines, 58 and EGCG induces apoptosis in H661 lung cancer cells. 59 …”