Electrochemotherapy causes caspase-independent necrotic-like death in pancreatic cancer cells
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Published version
Supplementary file 1
Date
2019-08-14
Authors
Fernandes, Philana
O'Donovan, Tracey R.
McKenna, Sharon L.
Forde, Patrick F.
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Published Version
Abstract
Pancreatic cancer represents a major challenge in oncology. Poor permeability of the pancreas and resistance to currently available therapies are impediments to improved patient survival. By transiently increasing cell membrane porosity and increasing drug uptake, Electrochemotherapy (ECT) has the potential to overcome these issues. In this study, we have evaluated the response of human and murine pancreatic cancer cells, in vitro, to electroporation in combination with Bleomycin, Cisplatin, or Oxaliplatin (ECT). The cytotoxic actions of all three drugs are potentiated when combined with electroporation in these cells. The biochemical and morphological changes post ECT are associated with immunogenic cell death that occurs with necroptosis rather than apoptosis. Moreover, ECT-induced cell death is rescued by Nec-1 suggesting that necroptosis may play a role in cell death mediated by cancer therapies.
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Keywords
ECT , Necroptosis , Apoptosis , ICD , Necrostatin-1
Citation
Fernandes, P., O’Donovan, T. R., McKenna, S. L. and Forde, P. F. (2019) 'Electrochemotherapy Causes Caspase-Independent Necrotic-Like Death in Pancreatic Cancer Cells', Cancers, 11(8), 1177. (21pp.) DOI: 10.3390/cancers11081177