Induction of apoptosis in human leukemic cells by ultrasonic low energy treatment

The biophysical effects of ultrasound have been frequently surveyed and its use has been proposed for some years, often in conjunction with other energy types (hyperthermia, radiation) for the treatment of cancer cells. This procedure requires long preparation, energy and the use of photosensitizers. In contrast, the technique described here, using diagnostic ultrasonic frequencies, requires a low acoustic power level and, in the absence of any chemical synergy, triggers apoptosis in leukemic cells. 2 hours after ultrasonic treatment of K562 cells, a sequence of events recognized as hallmarks of apoptosis was observed: depletion of glutathione, a drop of mitochondrial potential, translocation of phospatidylserine and, subsequently, loss of membrane integrity. These effects are not dependent on the formation of species issued from the sonolysis of the solvent medium. By using minute amounts of energy, necrosis generally associated with a high physiological stress is minimized (<10%). With successive irradiations, under the same conditions (7mW/ml, 20 sec) and at different intervals, K562 cell apoptosis was significantly increased (more than 25% after 2 irradiations). The higher sensitivity of K562 cells compared to normal blood cells allows a therapeutical index dose to be determined. Moreover, the sensitivity of ultrasound seems to depend on the cell type. K562 cells and B-CLL cells are the most sensitive compared to HL-60 cells and normal mononuclear blood cells. Thus, in our conditions, the cell damage induced by ultrasound in leukemic cells occurs through apoptosis and offers a mechanism of the smooth elimination of leukemia cells.