Direct Therapeutic Applications of Calcium Electroporation to Effectively Induce Tumor Necrosis

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 v...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2012-03, Vol.72 (6), p.1336-1341
Main Authors: FRANDSEN, Stine Krog, GISSEL, Hanne, HOJMAN, Pernille, TRAMM, Trine, ERIKSEN, Jens, GEHL, Julie
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - analysis
Animals
Antineoplastic agents
Biological and medical sciences
Calcium - administration & dosage
Calcium - therapeutic use
Carcinoma, Lewis Lung - chemistry
Carcinoma, Lewis Lung - drug therapy
Cell Line
Cricetinae
Electroporation
Fibroblasts - chemistry
Humans
Leukemia - drug therapy
Lung - chemistry
Lung Neoplasms - chemistry
Lung Neoplasms - drug therapy
Medical sciences
Mice
Mice, Nude
Pharmacology. Drug treatments
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-11-3782