Histone deacetylase Inhibitors have a profound proapoptotic activity in PNET cells

Histone deacetylase inhibitors (HDACIs) are emerging as a new class of antineoplastic agents. Our purpose was to investigate the effects of the HDACIs suberoyl anilide bishydroxamine, trichostatin A, and sodium butyrate against PNET cell lines. Treatment with HDACIs resulted in the time- and dose-dependent accumulation of acetylated histone proteins. Concomitantly, HDACIs provoked the dissipation of the mitochondrial membrane potential, activation of caspase-9 and -3 and, consequently, apoptotic cell death. In addition, HDACIs were found to interact synergistically with irradiation or apoptosis-inducing cytokines to elicit cell death in PNET cells. These findings raise the possibility that HDACIs may prove effective in the treatment of PNET. This work was supported by the Wilhelm Sander-Stiftung, Neustadt/Donau and by the Deutsche Krebshilfe.