Cladribine (2-CDA) is a well-known purine nucleoside analog against lymphoproliferative disorders. Entinostat, a selective class I histone deacetylase (HDAC) inhibitor, exerts anti-tumor activity in various cancers, including multiple myeloma (MM). We sought to determine whether cladribine and entinostat may exhibit synergistic anti-proliferative/anti-survival effects on MM cells. Here we showed that, in cell growth MTS assays, either cladribine or entinostat alone inhibited cell proliferation in a dose-dependent manner. The combinations of cladribine and entinostat significantly induced growth inhibition in MM cells tested. The combination index (CI) curves showed a synergistic effect between cladribine and entinostat. An apoptotic-ELISA and western blot analyses of caspase-3 and PARP revealed that entinostat in combination with cladribine exhibited a much more potent activity than either agent alone to promote the MM cells undergoing apoptosis in a dose and time-dependent manner. Collectively, our data suggest that combinations of entinostat and cladribine possess synergistic anti-proliferative/anti-survival activity in MM cells. Regimens consisting of entinostat and cladribine may represent novel therapeutic strategies against MM.

Citation Format: Bolun Wang, Hui Lyu, Bolin Liu. Entinostat in combination with Cladribine synergistically induces apoptosis in multiple myeloma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2043. doi:10.1158/1538-7445.AM2017-2043