Apoptotic Effect of Combination Treatment with a Proteasome Inhibitor, Lactacystin, and a Histone Deacetylase Inhibitor, Trichostatin A, on MCF-7 Cells / 대한해부학회지

ABSTRACT

Although much information has been accumulated about the synergistic interaction of proteasome inhibitors and HDAC inhibitors to induce apoptosis in a certain type of cells, much less is known currently about the underlying mechanism. This study was undertaken to explore the combination effect of a histone deacetylase inhibitor, TSA, and a proteasome inhibitor, lactacystin, on the induction of apoptosis. Pretreatment of TSA and subsequent treatment of lactacystin showed the strong antitumor activity and nuclear condensation. Western blot assay showed that combination treatment of TSA and lactacystin increased Bax/Bcl-2 ratio and decreased level of XIAP. Activation of caspase-7 and cleavage of PARP were demonstrated after the combination treatment. In combination treatment group, cell cycle arrest was induced at G2/M phase and abolished increase in proteasome activity. This study is elucidating the mechanims whereby targeting apoptotic machineries may help in directing therapeutic strategies.