Journal
CANCER RESEARCH
Volume 72, Issue 6, Pages 1336-1341Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-11-3782
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Funding
- Danish Cancer Society
- Danish Medical Research Council
- Lundbeck foundation
- Acta Oncologica Foundation
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Electroporation of cells with short, high-voltage pikes 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 clue 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. (C) 2012 AACR.
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