Transient inhibition of NF‐κB by DHMEQ induces cell death of primary effusion lymphoma without HHV‐8 reactivation

Abstract

Primary effusion lymphoma (PEL) is a refractory malignancy caused by human herpes virus 8 (HHV-8

Kaposi's Sarcoma-Associated Herpesvirus-Positive Primary Effusion Lymphoma Tumor Formation in NOD/SCID Mice Is Inhibited by Neomycin and Neamine Blocking Angiogenin's Nuclear Translocation

“…Similar to our results, blocking the NF-B pathway with Bay11-7082 has been shown to prevent or delay PEL tumor growth in NOD/SCID mice and prolong their disease-free survival (66). The therapeutic potential of blocking the NF-B pathway has been confirmed by blocking the proteosome with Bortezomib, using the new NF-B inhibitor dehydroxymethylepoxyquinomicin (DHMEQ), or using the biscoclaurine alkaloid cepharanthine (67)(68)(69)(70)(71). In all these studies, blocking the NF-B pathway induced the apoptosis of PEL.…”

The Effects of Heat Shock Protein 90 Inhibitors on Apoptosis and Viral Replication in Primary Effusion Lymphoma Cells

“…15,16) KSHV-encoded K1, viral glycoprotein, interacts with HSP90 for K1 dependent anti-apoptotic function. 17) Described above, NF-κB activation and HSP90 function are essential for the survival and growth of KSHV-infected lymphoma cells, 8,18,19) which is consistent with our data (Fig. 1).…”

Therapeutic effects of γ-irradiation in a primary effusion lymphoma mouse model

“…vfLIPmediated Nf-κB activation is necessary for the survival of PEL cells, and may cause them to become chemoresistant. Thus, the Nf-κB pathway represents an appropriate target for the molecular therapy of PEL, and several Nf-κB inhibitors are already potential candidates (24)(25)(26). One of these candidates, the proteasome inhibitor bortezomib, has been shown to inhibit Nf-κB activity and induce the apoptosis of PEL cell lines in vitro (27,28); however, bortezomib failed to control the progression of PEL in a clinical trial (29), indicating that …”