title: Direct therapeutic applications of calcium electroporation to effectively induce tumor necrosis.
abstract: 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.
authors.affiliation: Center for Experimental Drug and Gene Electrotransfer, Department of Oncology, Copenhagen University Hospital Herlev, Denmark.
authors.forename: Stine Krog
authors.initials: SK
authors.lastname: Frandsen
authors.forename: Hanne
authors.initials: H
authors.lastname: Gissel
authors.forename: Pernille
authors.initials: P
authors.lastname: Hojman
authors.forename: Trine
authors.initials: T
authors.lastname: Tramm
authors.forename: Jens
authors.initials: J
authors.lastname: Eriksen
authors.forename: Julie
authors.initials: J
authors.lastname: Gehl
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000008:administration & dosage / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000737:chemistry / Q000188:drug therapy*; D002460:Cell Line; D006224:Cricetinae; D018274:Electroporation; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D008168:Lung / Q000737:chemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude
chemical_list: D000255:Adenosine Triphosphate; D002118:Calcium