Figure 5.
Ricolinostat augments the in vitro antimyeloma activity of JQ1 in MM models. (A) Ricolinostat (RICO) enhances the ability of JQ1 to decrease c-MYC and BCL-2 expression, resulting in increased caspase-3 cleavage. MM cells were treated with 500 nM JQ1, 3 μM ricolinostat, or combinations for 24 hours. c-MYC, BCL-2, cleaved caspase-3, and acetylated α-tubulin levels were determined by immunoblotting. (B) Ricolinostat augments the proapoptotic effects of JQ1. LP-1 and OPM-2 MM cells were treated with 500 nM JQ1, 1 or 3 μM ricolinostat, or combinations for 48 hours. Apoptosis was determined by active caspase-3 or PI-FACS analysis. (C-D) Ricolinostat and vorinostat (VOR) enhance the anticancer activity of JQ1 in MM cell lines and primary CD138+ cells collected from patients with MM (n = 10). Cells were treated with 500 nM JQ1, 1 μM vorinostat, 3 μM ricolinostat, or combinations for 72 hours. Cell viability was determined by MTT assay. Data are shown as mean ± SD; n = 3. *Indicates a significant difference from control; **indicates single-agent treatment groups.