Curcumin Inhibits Activation of Vγ9Vδ2 T Cells by Phosphoantigens and Induces Apoptosis Involving Apoptosis-Inducing Factor and Large Scale DNA Fragmentation

Abstract

Curcumin, in addition to its role as a spice, has been used for centuries to treat inflammatory disorders. Although the mechanism of action remains unclear, it has been shown to inhibit the activation of NF-κB and AP-1, transcription factors required for induction of many proinflammatory mediators. Due to its low toxicity it is currently under consideration as a broad anti-inflammatory, anti-tumor cell agent. In this study we investigated whether curcumin inhibited the response of γδ T cells to protease-resistant phosphorylated derivatives found in the cell wall of many pathogens. The results showed that curcumin levels ≥30 μM profoundly inhibited isopentenyl pyrophosphate-induced release of the chemokines macrophage inflammatory protein-1α and -1β and RANTES. Curcumin also blocked isopentenyl pyrophosphate-induced activation of NF-κB and AP-1. Commencing around 16 h, treatment with curcumin lead to the induction of cell death that could not be reversed by APC, IL-15, or IL-2. This cytotoxicity was associated with increased annexin V reactivity, nuclear expression of active caspase-3, cleavage of poly(ADP-ribose) polymerase, translocation of apoptosis-inducing factor to the nucleus, and morphological evidence of nuclear disintegration. However, curcumin led to only large scale DNA chromatolysis, as determined by a combination of TUNEL staining and pulse-field and agarose gel electrophoresis, suggesting a predominantly apoptosis-inducing factor-mediated cell death process. We conclude that γδ T cells activated by these ubiquitous Ags are highly sensitive to curcumin, and that this effect may contribute to the anti-inflammatory properties of this compound.

p16 gene transfer increases cell killing with abnormal nucleation after ionising radiation in glioma cells

“…Induction of cleavage of chromatin in U251MG cells was determined by PFGE, as described elsewhere (Hwang et al, 2000;Cipriani et al, 2001). In breif, U251MG cells were infected with Axhp16 or Ax-mock after irradiation and collected by trypsinisation after 5 days of incubation.…”

“…We investigated the cleavage of chromatin by examining the formation of 50/300-kb fragments, which are generated during the early stages of apoptosis and can be identified by PFGE (Khodarev et al, 1998;Hwang et al, 2000;Cipriani et al, 2001). The 50/300-kb fragments were formed in irradiated noninfected and Ax-mock-infected U251MG cells, but not in nonirradiated U251MG cells.…”

Hepatoprotective and immunomodulatory properties of aqueous extract of Curcuma longa in carbon tetra chloride intoxicated Swiss albino mice

“…Anti-inflammatory activity of turmeric oil has been reported on pepper 榮 s model [15] . The volatile oil of C. longa was effective in anti-inflammatory and antihyaluronidase action [16] .…”

“…for 7 days. Second group was fed orally the aqueous extract of turmeric at a dose of 50 mg/kg bw for 15 days. The third group was given both the turmeric extract (for 15 days, orally) and CCl 4 (for last 7 days, i.p.).…”

Mechanism of Action of Nigella sativa on Human Colon Cancer Cells: the Suppression of AP-1 and NF-κB Transcription Factors and the Induction of Cytoprotective Genes

“…non-oligonucleosomal) DNA fragmentation (Susin et al, 2000), which may explain why we could not see DNA fragmentation or caspase-3 activation. The induction of programmed cell death without caspase activation or DNA fragmentation has been attributed to other chemotherapeutic agents, such as curcumin and Matrine (Cipriani et al, 2001;Zhou et al, 2014). Similar to these agents, it seems that CSENS bestows, as yet unknown, caspase-independent pathway to impose its apoptogenic potentiality.…”