Modulating Apoptosis in Cancer Therapy with Ultrasound and High-Intensity Nanosecond Electric Pulses
Ultrasound can induce apoptosis and enhance apoptosis attributable to anticancer drugs, in which cavitation plays the leading role. Cavitation leads to the production of reactive radicals and shear forces, which insult DNA and mitochondria, initiating apoptosis via the cytochrome c–caspase 3 pathway. Cavitation permeabilizes the cell membrane, thereby increasing the intracellular drug level and enhancing the efficacy of the cytotoxic drug. Ultrasonically chemotherapeutic sensitization is effective in both chemosensitive and chemoresistant cancer cells. The biological responses to high-intensity electric pulses are dependent on the voltage applied and the pulse length. Nanosecond electric pulses can pass through plasma and nuclear membranes to create sufficiently high voltages in the cytoplasm and in the nucleus with intact plasma and nuclear membranes, thereby impacting mitochondria or DNA, resulting in apoptosis. Nanosecond electric pulses may induce apoptosis via the intrinsic or the extrinsic pathway, and electrical and mechanical mechanisms may be involved. Both ultrasound and electric pulses can be delivered precisely into preselected tissues, so these two techniques can be developed for targeted cancer therapy.
KeywordsUltrasound Apoptosis Electric pulses Cancer therapy Cancer Nanosecond electric pulses
The work in our laboratory was supported by grants from the Natural Science Foundation of China (11174376, 30972830) and the Natural Science Foundation of Chongqing (CSTC 2009BA5049).
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