RESUMO
AIM: To determine the phenotypic effects of belinostat (bel) and bortezomib (bor) against pancreatic cancer (PC) and hepatocellular cancer (HCC) cell lines. MATERIALS AND METHODS: Antiproliferative effects were assessed using a sulforhodamine B assay. Synergy was evaluated using the Chou and Talalay method. Apoptosis was measured by caspase-3/-7 activity and PARP cleavage. Downstream effector proteins were detected via immunoblotting. Quantitative nuclear magnetic resonance (NMR)-based metabolomics analysis was performed. RESULTS: There were single-agent antiproliferative effects against PC and HCC cell lines; the combination of bel and bor (bel+bor) had a synergistic effect. There was up to a 45-fold induction of apoptosis over the control. Post-treatment cell death was associated with p21 up-regulation, more pronounced with treatment with bel+bor. Treatment with bel+bor enhanced hyperacetylation of histone H3 over single-agent bel. A metabolic signature was established for treatments with bor and bel+bor. CONCLUSION: The combination of bel+bor displayed significant antiproliferative activity against PC and HCC cell lines, with exhibiting synergistic antiproliferative and proapoptotic patterns even at suboptimal single-agent doses.
