Direct Therapeutic Applications of Calcium Electroporation to Effectively Induce Tumor Necrosis

Stine Krog Frandsen1, Hanne Gissel2, Pernille Hojman3, Trine Tramm4, Jens Eriksen1,5, and Julie Gehl1

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  lectroporation with isotonic calcium can achieve highly effective cancer cell kill in vivo. Calciumelectroporation 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. Cancer Res; 72(6); 1336–41. 2012 AACR.

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