Mitochondrial Apoptosis and FAK Signaling Disruption by a Novel Histone Deacetylase Inhibitor, HTPB, in Antitumor and Antimetastatic Mouse Models
Figure 1
Effect of HTPB on cell viability and on the biomarkers associated with broad inhibition on numerous HDACs.
(A) Chemical structure of HTPB (upper left). Dose-dependent effects of HTPB on cell viability in IMR90, H1299, and A549 cells (lower left). Cells were treated with 0.5–10 µM of HTPB for 48 hours, and cell viability was assessed by MTT assay. A known HDAC inhibitor, SAHA, was used for comparison. (B) HTPB suppressed activities of class I (HDAC1 and HDAC8), class II (HDAC4 and HDAC6), and class IV (HDAC11) HDACs in A549 cells. Data represent mean ± SEM from three independent experiments. *** P<0.001. Dose-dependent effects (C) and time-dependent effects (D) of HTPB on the histone and non-histone proteins. SAHA was included for comparison. (E) HTPB induced acetylation of histone H3 and H4 without affecting the total protein levels of HDAC1 and HDAC 6. In addition, HTPB induced p21 protein expression in both A549 (p53 wild-type) and H1299 (p53 null) cells. The immunoblots shown are representatives of three independent experiments.