Stine Krog Frandsen1, Hanne Gissel2, Pernille Hojman3, Jens Eriksen4, Julie Gehl5. 1. Center for Experimental Drug and Gene Electrotransfer, Department of Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, 2730 Herlev, Denmark. 2. Institute of Biomedicine, Aarhus University, Building 1160, Ole Worms Allé 4, 8000 Aarhus C, Denmark. 3. 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. Center for Experimental Drug and Gene Electrotransfer, Department of Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, 2730 Herlev, Denmark. Electronic address: Julie.Gehl@regionh.dk.
Abstract
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.
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, humanleukemia; and murineLewis 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.
Authors: Emilie Louise Hansen; Esin Bengisu Sozer; Stefania Romeo; Stine Krog Frandsen; P Thomas Vernier; Julie Gehl Journal: PLoS One Date: 2015-04-08 Impact factor: 3.240
Authors: Mille Vissing; John Ploen; Mascha Pervan; Kitt Vestergaard; Mazen Schnefeldt; Stine Krog Frandsen; Søren Rafael Rafaelsen; Christina Louise Lindhardt; Lars Henrik Jensen; Achim Rody; Julie Gehl Journal: BMJ Open Date: 2021-06-16 Impact factor: 2.692