Figure 4. HDAC inhibition activates the ER stress responsive element in LNCaP carcinoma cells in a dose-dependent manner.

A. Single-cell clones of LNCaP cells stably transduced with an ER stress responsive element driving firefly luciferase expression were exposed to vorinostat or entinostat, at the designated concentrations, or DMSO controls, as described in Materials and Methods. At the end of treatment, firefly and renilla luciferase activities were determined. Data are shown as the ratio of firefly luciferase activity relative to that of control renilla luciferase within each well, further normalized to DMSO control. Results are presented as mean ± S.E.M. from 4-6 replicate wells, and are representative of two independent experiments. B. Parental LNCaP prostate carcinoma cells were exposed to vorinostat (3 μM), entinostat (500 nM) or to vehicle (DMSO) controls as described in Materials and Methods, prior to being used as targets for antigen-specific CTL lysis using PSA-specific CD8⁺ T cells as effector cells (E:T = 30:1). Results are presented as mean ± S.E.M. from 6 replicate wells. Asterisks denote statistical significance relative to controls (P < 0.05). C. Schematic representation of immunogenic modulation induced by HDAC inhibition in human carcinoma cells.