Parthenolide induces apoptosis and lytic cytotoxicity in Epstein-Barr virus-positive Burkitt lymphoma

Abstract

Burkitt lymphoma (BL) has been reported to be strongly associated with Epstein-Barr virus (EBV) infection. The fact that EBV is generally present in cancer cells but rarely found in healthy cells represents an opportunity for targeted cancer therapy. One approach is to activate the lytic replication cycle of the latent EBV. Nuclear factor (NF)-κB is thought to play an essential role in EBV lytic infection. Elevated NF-κB levels inhibit EBV lytic replication. Parthenolide (PN) is a sesquiterpene lactone found in medicinal plants, particularly in feverfew ( Tanacetum parthenium ). The aim of the present study was to analyze the effect of PN on the survival of Raji EBV-positive lymphoma cells. Raji cells were treated with 0, 4 or 6 μmol/l PN for 48 h. MTT assay and western blot analysis were performed to evaluate the findings. Results showd that PN suppressed the growth of the EBV-positive BL cell line, Raji, and activated the transcription of BZLF1 and BRLF1 by inhibiting NF-κB activity. Most notably, when PN was used in combination with ganciclovir (GCV), the cytotoxic effect of PN was amplified. These data suggest that the induction of lytic EBV infection with PN in combination with GCV may be a viral-targeted therapy for EBV-associated BL.

Regulation of Epstein–Barr virus reactivation from latency

“…first reported that NF‐κB has an inhibitory role in the lytic replication of γ‐herpesvirus, including EBV, in 2003 . This report was followed by similar reports from other groups . The JAK/STAT pathway also reportedly negatively regulates the EBV lytic cycle .…”

Parthenolide Influences <b><i>Herpes simplex</i></b> v<b><i>irus 1</i></b> Replication in vitro

“…Epstein-Barr-infected cells that were treated with parthenolide exhibited an increase in the expression of caspase-8 and caspase-9 and decrease in the accumulation of p65 subunit in the nucleus [9]. Houttuynia cordata extract blocked activation of the NF-κB pathway in HSV-1-infected cells and in cells that were stimulated with TNF-α [14].…”

“…A previous study found that parthenolide altered the expression of the intrinsic (caspase-9) and extrinsic (caspase-8) pathways [9]. Both pathways converge inside the cell.…”

“…The evaluation of caspase expression was performed as described previously [9], with minor modifications. Six-well plates were prepared with Vero cells, infected with HSV-1 (KOS strain), and treated for 24 h with 2.5 μg/mL parthenolide (EC 50 ).…”

“…Parthenolide has antiparasitic [4,5], antiviral, and anti-inflammatory effects. It also has antineoplastic activity in vitro and induces apoptosis in neoplastic cells, thus interfering with signaling pathways [6][7][8][9].…”