Chemopreventive Agent Resveratrol, a Natural Product Derived From Grapes, Triggers CD95 Signaling-Dependent Apoptosis in Human Tumor Cells

Abstract

Resveratrol, a constituent of grapes and other food products, has been shown to prevent carcinogenesis in murine models. We report here that resveratrol induces apoptotic cell death in HL60 human leukemia cell line. Resveratrol-treated tumor cells exhibit a dose-dependent increase in externalization of inner membrane phosphatidylserine and in cellular content of subdiploid DNA, indicating loss of membrane phospholipid asymmetry and DNA fragmentation. Resveratrol-induced cell death is mediated by intracellular caspases as observed by the dose-dependent increase in proteolytic cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and the ability of caspase inhibitors to block resveratrol cytotoxicity. We also show that resveratrol treatment enhances CD95L expression on HL60 cells, as well as T47D breast carcinoma cells, and that resveratrol-mediated cell death is specifically CD95-signaling dependent. On the contrary, resveratrol treatment of normal human peripheral blood lymphocytes (PBLs) does not affect cell survival for up to 72 hours, which correlates with the absence of a significant change in either CD95 or CD95L expression on treated PBLs. These data show specific involvement of the CD95-CD95L system in the anti-cancer activity of resveratrol and highlight the chemotherapeutic potential of this natural product, in addition to its recently reported chemopreventive activity. © 1998 by The American Society of Hematology.

Regulatory effect of resveratrol and prednisolone on MDR1 gene expression in acute lymphoblastic leukemia cell line (CCRF‐CEM): An epigenetic perspective

“…In a previous study made by Clement et al, it was demonstrated that resveratrol can induce programmed cell death in HL60 cells through death receptor . Similarly, Surh et al revealed the induction of apoptosis in HL60 cells by resveratrol .…”

“…In a previous study made by Clement et al, it was demonstrated that resveratrol can induce programmed cell death in HL60 cells through death receptor. 26 Similarly, Surh et al revealed the induction of apoptosis in HL60 cells by resveratrol. 31 In this regard, Tsan et al also showed that the death receptors are not engaged in apoptosis induction and this programmed death may be a consequence of other different ways.…”

“…25 It is clarified that resveratrol can make the resistant malignant cells sensitive to therapy through several mechanisms. It increases the expression of CD95L and death receptors mediated apoptosis, 26 modifies NF-KB pathway and induces programmed cell death, 27 modifies STAT3 expression by reducing the function of tyrosine kinase Src and regulates the survivin induction (target gene of STAT3), and strengthens the p53 operation and NO production. [28][29][30] Furthermore, GCs act via a ligand activated transcription factor known as GC receptor (GR) residing in the cytoplasm which following the ligand binding and translocation into nucleus, function as gene expression regulator through binding with certain DNA response elements.…”

The Effects of Resveratrol Targeting MicroRNA-4325P/PDGF-B to Regulate Tumor Angiogenesis in Osteosarcoma Microenvironment

“…In addition, several publications have revealed an elevated level of PDGF expression in clinical OS specimens. 18,25,26…”

“…In addition, several publications have revealed an elevated level of PDGF expression in clinical OS specimens. 18,25,26 As seen in Figure 6, the expression of microRNA-4325p is associated with the angiogenesis induced by resveratrol in OS cells, which was thought to be involved in its regulation. Therefore, in this investigation, the effects were investigated of resveratrol on the putative target genes of microRNA-4325p by transiently transfecting MG-63 cells with the mimic or inhibitor, control miRNA or resveratrol (20 µM), followed by total RNA and real-time transcription-PCR analysis of the resulting RNA.…”