Cell death in human acute myelogenous leukemic cells induced by pyrrolidinedithiocarbamate

Pyrrolidinedithiocarbamate (PDTC) is a metal chelating compound, which exerts both pro-apoptotic effect and pro-oxidant activity on many cells. Our objective was to investigate whether PDTC was able to interfere with apoptotic process in leukemic and normal bone marrow CD34⁺ cells. Since hematopoietic growth factors stimulate growth and differentiation and prevent apoptosis, we therefore studied the effect of growth factors pretreatment, such as interleukin-3 and granulocyte-macrophage colony stimulating factor, in human myeloid CD34⁺ cells to evaluate whether they protect the cells from the apoptotic action of PDTC.We revealed that PDTC exerted an apoptotic effect in leukemic CD34⁺ cells. This effect was dependent on the ability of this compound to generate the oxidation of cellular glutathion to its disulphide and consequently to induce an intracellular oxidative stress. Hematopoietic growth factors did not protect cells from apoptosis induced by previous treatment with PDTC. The ability of PDTC to induce apoptosis was restricted to acute myelogenous leukaemia CD34⁺ cells, since normal CD34⁺ cells were insensitive to the pro-oxidant effect of PDTC.These findings imply that normal cells are equipped with mechanisms by which they respond differently to PDTC effects with respect to leukemic cells.