In vitro study | Resminostat[HCl], a potent inhibitor, is a recombinant of HDAC1,3 and 6 isozymes that competitively bind to the matrix. It acts on MM cells and can induce high acetylation of histone H4. Resminostat acts at low micromolar concentrations on MM cell lines (OPM-2,NCI-H929,U266) to prevent cell growth and strongly induce apoptosis, consistent with the effect on primary MM cells. At 1 μm, Resminostat acts on the MM cell line, inhibiting cell proliferation and inducing G0/G1 phase arrest of the cell cycle at OPM-2,NCI-H929, u266. The cell lines were accompanied by decreased levels of cyclin D1,CDC25A,CDK4 and Rb and up-regulation of the p21 gene. Resminostat directs interference with the Akt signaling pathway by reducing phosphorylation of 4E-BP1 and p70S6K. Treatment with Resminostat resulted in increased levels of Bim and Bax protein expression and a decrease of Bcl-xL levels. Resminostat activates Caspases 3, 8, and 9. In addition, Resminostat synergizes with Melphalan and Proteasome inhibitors bortezomib and S-2209. |