1 Department of Biomedicine - Forskning og uddannelse, Vest, Department of Biomedicine, Health, Aarhus University2 Center for Experimental Drug and Gene Electrotransfer, Department of Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, 2730 Herlev, Denmark3 Centre of Inflammation and Metabolism, Department of Infectious Diseases, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark.4 Center for Experimental Drug and Gene Electrotransfer, Department of Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, 2730 Herlev, Denmark; Department of Pathology, Naestved Sygehus, Ringstedgade 61, 4700 Naestved, Denmark.5 Department of Biomedicine - Forskning og uddannelse, Vest, Department of Biomedicine, Health, Aarhus University
a comparison of bleomycin and calcium, calcium compounds, and pulsing conditions
BACKGROUND: Electroporation with calcium (calcium electroporation) can induce ATP depletion-associated cellular death. In the clinical setting, the cytotoxic drug bleomycin is currently used with electroporation (electrochemotherapy) for palliative treatment of tumors. Calcium electroporation offers several advantages over standard treatment options: calcium is inexpensive and may readily be applied without special precautions, as is the case with cytostatic drugs. Therefore, details on the use of calcium electroporation are essential for carrying out clinical trials comparing calcium electroporation and electrochemotherapy. METHODS: The effects of calcium electroporation and bleomycin electroporation (alone or in combination) were compared in three different cell lines (DC-3F, transformed Chinese hamster lung fibroblast; K-562, human leukemia; and murine Lewis Lung Carcinoma). Furthermore, the effects of electrical pulsing parameters and calcium compound on treatment efficacy were determined. RESULTS: Electroporation with either calcium or bleomycin significantly reduced cell survival (p<0.0001), without evidence of a synergistic effect. Cellular death following calcium or bleomycin treatment occurred at similar applied voltages, suggesting that similar parameters should be applied. At equimolar concentrations, calcium chloride and calcium glubionate resulted in comparable decreases in cell viability. CONCLUSIONS: Calcium electroporation and bleomycin electroporation significantly reduce cell survival at similar applied voltage parameters. The effect of calcium electroporation is independent of calcium compound. GENERAL SIGNIFICANCE: This study strongly supports the use of calcium electroporation as a potential cancer therapy and the results may aid in future clinical trials.
Biochimica Et Biophysica Acta, 2013, Vol 1840, Issue 3, p. 1204-8