Bortezomib combines with suberoylanilide hydroxamic acid (SAHA) to synergistically induce caspase-dependent apoptosis and blocks SAHA's activation of EBV lytic cycle in nasopharyngeal carcinoma

Abstract

Poster Session 1 - Vaccines and Anti-Viral Therapeutics: no. 3.13Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), could induce Epstein-Barr virus (EBV) lytic cycle and apoptosis in EBV-positive nasopharyngeal carcinoma (NPC) cells. In this study, we investigated the effects of combining a proteasome inhibitor, bortezomib, with SAHA in the treatment of NPC cells. Synergistic killing of a panel of EBV-positive NPC cells upon treatment with various combinations of bortezomib (0, 7.5, 15, 30, 60 and 120 nM) and SAHA (0, 0.625, 1.25, 2.5, 5 and 10 uM) was demonstrated by MTT assay and isobologram analysis. The synergistic killing was due to apoptosis as demonstrated by markedly increased sub-G1, annexin V-positive and TUNEL-positive cell populations. Strong proteolytic cleavage of PARP, caspase-3, -7 and -9 and increased reactive oxygen species …postprin