Electroporation of cells with short, high-voltage pulses causes a transient permeabilization of cell membranes that permits passage of otherwise nonpermeating
ions and molecules. In this study, we illustrate how electroporation with isotonic
calcium can achieve highly effective
cancer cell kill in vivo.
Calcium electroporation elicited dramatic antitumor responses in which 89% of treated
tumors were eliminated. Histologic analyses indicated complete
tumor necrosis. Mechanistically,
calcium electroporation caused acute
ATP depletion likely due to a combination of increased cellular use of
ATP, decreased production of
ATP due to effects on the mitochondria, as well as loss of
ATP through the permeabilized cell membrane. Taken together, our findings offer a preclinical proof of concept for the use of electroporation to load
cancer cells with
calcium as an efficient anticancer treatment. Electroporation equipment is already used clinically to enhance the delivery of
chemotherapy to superficial
tumors, with trials on internal
tumors in progress, enabling the introduction of
calcium electroporation to clinical use. Moreover, the safety profile, availability, and low cost of
calcium facilitate access to this technology for many
cancer patients in developed and developing countries.