Therapeutic ultrasound induces apoptosis in p53 positive and p53 negative malignant hemopoietic cell lines

None of the modalities currently employed to induce apoptosis involves the use of ultrasound energy. We have demonstrated (Cancer Res. 60: 1014, 2000) that selected physical parameters utilized in therapeutic ultrasound (ULS) application resulting in cavitation process induce an apoptotic cell death. The aim of the present study was to investigate ULS application with rational selected physical parameters to optimize ultrasound cavitation- induced cell death and to determine whether apoptosis is involved. High intensity focussed ULS sonication was delivered with an induction of transient cavitation and intensity of 54 W/cm2 to malignant T and B lymphocyte-derived cell lines expressing p53 as Raji, Jurkat and NALM-6 as well as myeloid leukemia cell lines p53 negative HL-60, K562, U937. Here we present evidence that much of the cell damage surviving ULS exposure appears to occur through an apoptotic mechanism. Morphological alterations of apoptotic cells involve nuclear fragmentation and apoptotic body formation. Positive identification of apoptotic cells was based also on the detection of nuclear DNA strand break and changes in the surface of treated cells undergoing apaptosis expressed by the breakup of phosphatidylserine from the inner to the outer side of the membrane layer. In summary, after ULS exposure malignant hemopoietic cell lines can be induced to undergo apoptosis by p53-dependent and p53-independent apoptotic pathways.