NVP-LAQ824 induces time- and dose-dependent histone hyperacetylation, p21 up-regulation, and PARP cleavage. (A-B) NVP-LAQ824 induced both a time- and dose-dependent increase in histone acetylation at concentrations as low as 0.01 μM after 24 hours, and as early as 2 hours with 1 μM NVP-LAQ824. Immunoblotting with antiactin Ab confirmed equivalent protein loading. Ac-H4 indicates acetylated histone 4. (C) p21 up-regulation was evident as early as 4 hours in treated cells, but returned to below baseline by 8 hours. (D) Densitometric analysis demonstrated a 36% increase in p21 expression at 4 hours. (E) PARP cleavage of an 85-kDa product was observed at 8 hours, consistent with apoptosis. FL indicates full-length fragment; CF, cleavage fragment.