Effect of the Histone Deacetylase Inhibitor Trichostatin A in Human Peripheral Blood Lymphocytes as a Function of Donor Age

摘要

The histone deacetylase inhibitor trichostatin A (TSA) is apromising agent for the treatment of certain types of cancers alone or insynergistic combination with other anticancer agents. One of the advan-tages of the use of histone deacetylase inhibitors, such as TSA, is that itseffects have been found to be more potent toward cancer cells comparedto normal cells. The effect of anticancer agents on the immune system,and on lymphocytes in particular, is of major importance to the success ofanticancer regimens. In this respect, information documenting the effectof such agents on normal lymphocytes compared to malignant cells maybe of significant value for the successful designing of clinical protocols.Moreover, the parameter of age may be a factor in the differential effectsof such protocols. Histone deacetylase inhibitors lead to the accumulationof acetylated histones and, depending on the cell type, may induce eitherapoptosis, cell cycle arrest, or differentiation. Previous work from ourlab has shown that TSA induces the accumulation of histone H4 acety-lation and apoptosis in human peripheral blood lymphocytes. In lightof the above, we have extended our investigation of the effects of TSAon human lymphocytes to include the parameter of age, which has notbeen previously studied. Our results show that TSA induces apoptosis oflymphocytes from donors of all age groups, but no age-related changesin the levels of apoptosis are observed.