Ultrafast high voltage pulses have been shown to penetrate into living cells to permeabilize intracellular organelles and release Ca2+ from the endoplasmic reticulum. They provide a new approach for physically targeting intracellular organelles with many applications, including initiation of apoptosis, enhancement of gene transfection efficiency and inhibiting tumor growth. Here we show that 40 kV/cm electric field pulses 300 nanoseconds in duration can rapidly stimulate pyknosis, reduce blood flow and trigger apoptosis in murine melanoma tumors in vivo with a total field exposure time of less than a millisecond. Four treatments of 100 pulses each results in a mean tumor size regression of 90% within two weeks. This new therapy is the first to simultaneously trigger pyknosis and reduce tumor blood flow. We also measure caspase activation and DNA fragmentation within three hours after the pulse treatment. The main advantages of this technique are: 1) It provides highly localized targeting of tumor cells with only minor effects on overlying skin; 2) It is a drug-free therapy; 3) It involves a very low energy of 0.2 Joules/pulse applied to the tissue that will increase the temperature of the treated region by no more than 2-4 oC.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]