Panobinostat(LBH-589) is a broad-spectrum HDAC inhibitor; low nanomolar concentrations (IC50=5-20 nM) of LBH589 induced cell-cycle arrest, apoptosis, and histone (H3K9 and H4K8) hyperacetylation in MOLT-4 and Reh cell.
LBH589 induces apoptosis among MOLT-4 and Reh cells in a time- and dose-dependent manner. Moreover, LBH589 is more potent in MOLT-4 than in Reh cells. LBH589 markedly prevents the growth of both MOLT-4 and Reh cells in a dose-dependent manner at 48 hours. LBH589 treatment causes a 2- to 3-fold increase in the number of cells in the G2/M phase of the cell cycle compared with the control cells. LBH589 is associated with induction of histone H3K9 and histone H4K8 acetylation as well as decreasing levels of c-Myc expression in a dose-dependent manner. LBH589 treatment also increases the levels of p21 expression. LBH589 treatment also decreases the levels of c-Myc after an initial increase at the lowest dose (10 nM) in Reh cells. In addition, LBH589 gives rise to substantial increases in mRNA levels of proapoptosis and DNA repair genes. LBH589 induces increased levels of acetylated histone H3 and H4 at the GADD45G promoter.
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