Cytotoxic and apoptotic effects of echinomycin on murine leukemia cells

A number of anticancer-chemotherapeutic agents induce cell death through the process of apoptosis. Effects of echinomycin, an anticancer agent on cancer progression, were investigated in P388 murine leukemia cells. First, according to the results of cytotoxicity measurement, IC₅₀ of echinomycin was 1.12 nM, a relatively lower value than the other examined anticancer agents, mitomycin-C and etoposide. Second, the DNA fragmentation assay for echinomycin-treated cells exhibited that echinomycin was able to induce apoptosis in a shorter period of time and with a lower dose than mitomycin-C or etoposide. The data of DNA fragmentation were quite comparable to those of cytotoxicity measurement. Finally we showed that mitogen-activated protein (MAP) kinase, a key protein in cell mitosis, was translocated into the nucleus from the cytosol after treatment with echinomycin. These findings suggest that a MAP kinase-related process may be involved in apoptosis induced by echinomycin.